Phagocytosis and Cytokinesis: Do Cells Use Common Tools to Cut and to Eat? Highlights on Common Themes and Differences


  • Chantal Deschamps,

    Corresponding author
    1. CNRS, UMR 8104, Paris, France
    2. Université Paris Descartes, Sorbonne Paris Cité, Paris, France
    • Inserm, U1016, Paris, France
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  • Arnaud Echard,

    Corresponding author
    1. Institut Pasteur, Membrane Traffic and Cell Division Laboratory, Paris cedex 15, France
    2. CNRS URA2582, Paris, France
    • Inserm, U1016, Paris, France
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  • Florence Niedergang

    Corresponding author
    1. CNRS, UMR 8104, Paris, France
    2. Université Paris Descartes, Sorbonne Paris Cité, Paris, France
    • Inserm, U1016, Paris, France
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  • All authors contributed equally to this work.

Corresponding authors: Chantal Deschamps,; Arnaud Echard, and Florence Niedergang,


Eukaryotic cells with specialized functions often use and adapt common molecular machineries. Recent findings have highlighted that actin polymerization, contractile activity and membrane remodelling with exocytosis of internal compartments are required both for successful phagocytosis, the internalization of particulate material and for cytokinesis, the last step of cell division. Phagocytosis is induced by the triggering of specific cell surface receptors, which leads to membrane deformation, pseudopod extension and contraction to engulf particles. Cytokinesis relies on intense contractile activity and eventually leads to the physical scission of sister cells. In this review, shared features of signalling, cytoskeletal reorganization and vesicular trafficking used in both phagocytosis and cytokinesis will be described, but non-common mechanisms and questions that remain open in these dynamic areas of research are also highlighted.


It has been proposed that cytokinesis, the last step of cell division, primary cilium or immune synapse formation use common mechanisms and pathways [1]. Despite shared features, a precise comparison between cytokinesis and phagocytosis has never been discussed, but appears timely in light of recent results on membrane and cytoskeleton remodelling.

Phagocytosis is the mechanism of internalization used by specialized cells of the immune system such as macrophages, dendritic cells and polymorphonuclear neutrophils to engulf large particles, micro-organisms and cell debris [2, 3]. It is induced by cross-linking of receptors and intense F-actin polymerization that generate the force driving membrane extension. This is accompanied by active membrane remodelling and focal exocytosis where internal membranes are targeted to release membrane tension, to drive efficient pseudopod extension and phagosome formation. Contractile activity relying on myosins is necessary for pseudopod extension and final closure of the phagosome, which is the least understood part. Phagocytosis can be initiated by distinct receptors that trigger different signalling pathways and molecular mechanisms.

Cytokinesis is the final step of cell division whereby the mother cell is physically divided into two independent daughter cells [4, 5]. The initiation of cytokinesis is not triggered with surface receptor stimulation, but is controlled internally during mitotic exit. As with phagocytosis, cytokinesis requires intense contractile activity. A ‘contractile ring’ made of F-actin filaments and myosin II assembles equatorially at the cell cortex and its subsequent constriction leads to the ingression of a cleavage furrow. Following these early events, an intercellular bridge connects the sister cells. Abscission has been the recent focus of a number of studies, which has greatly increased our understanding of the process. Membrane remodelling, local exocytosis and endocytosis contribute to the late steps of cytokinesis.

This review will highlight the shared molecular machineries implicated in cytoskeleton dynamics and membrane trafficking during both early steps of phagocytosis and late stages of cytokinesis in metazoans, essentially in mammalian cells. We will address recent advances in the understanding of membrane trafficking, signal and cytoskeleton involved in both processes. As the functional purposes of phagocytosis and cytokinesis, as well as the scale of membrane deformation and topology that occur during these processes are quite different, we will also focus on differences before discussing some unanswered questions.

Cytoskeleton Dynamics During Cytokinesis and Phagocytosis

Plasma membrane deformation associated with an actin ring-like structure

Deformation of the plasma membrane during phagocytosis and cytokinesis relies on transient modifications in both the F-actin and microtubule cytoskeleton networks. One of these modifications is the formation of a specific F-actin ring-like structure necessary to drive internalization of particles during phagocytosis (the phagocytic cup) and ingression of the cleavage furrow during cytokinesis (the actomyosin contractile ring) (Figure 1).

Figure 1.

Plasma membrane deformation through signalling to F-actin polymerization during phagocytosis and cytokinesis. Schemes show phagocytic cup of FcR-mediated (left), CR3-mediated phagocytosis (middle) and furrow formation (right). Actin is in green, microtubules are in grey and plasma membrane in dark blue. Discontinuated boxes correspond to views through a section at indicated positions. During FcR-mediated phagocytosis, Cdc42 recruits N-WASP, which stimulates actin nucleation by the Arp2/3 complex (continuous actin cup in green). Downstream of Rac, the Wave complex contributes to further actin remodelling together with the LIM Kinase, which phosphorylates and inhibits cofilin. Rac also triggers the phosphorylation of myosin chains that control phagosomal contractility. During CR3-mediated phagocytosis, RhoA activates Rho Kinase (ROK), the Arp2/3 complex and the formin mDia1 (punctate actin in green). RhoG is implicated in both CR3- and FcR-mediated phagocytosis. During cytokinesis, RhoA-dependent signalling controls F-actin polymerization, ROK and Myosin II activation necessary for contractility in the cleavage furrow, using a pathway similar to what is downstream of CR3. Electron microscopy images show one opsonized red blood cell (red) phagocytosed by macrophage via FcR (left) or via CR3 (middle). Bars, 1.5 µm. Fluorescent images (right) of Septin2 (green), acetyl-tubulin (red) and DAPI (blue) during furrow ingression. Bar, 5 µm.

The phagocytic cup is defined by actin polymerization in a network that allows membrane extension around the particle to internalize. It was initially described as being different for the two best-characterized types of phagocytosis, i.e. FcR- and CR3-mediated phagocytosis the former leading to pseudopod extensions while the latter was described as the particle ‘sinking’ into the cell [6]. More recently, however, ruffle formation was observed also in CR3 phagocytosis [7, 8]. Contractile activities are implicated in the closure of the phagosome. During cytokinesis, the actomyosin contractile ring is a meshwork of actin filaments rather than a continuous F-actin ‘ring’, which can be asymmetric in some cell types and does not contract concomitantly around the cell equator [9, 10]. The ring diameter progressively shrinks, with actin filaments and myosin II displaying high turnover [11-13]. The topologies are different during cytokinesis and phagocytosis, with the actomyosin ring pulling the plasma membrane in a constricted region during cytokinesis and the actin network pushing the membrane during the early steps of phagocytosis. However, the last steps of phagocytosis, especially CR3-mediated [14], involve constriction of a ring-like structure that might be very similar to the contractile ring involved in cytokinesis.

Control of actin polymerization, role of GTPases

The amount of actin filaments locally increases at the cytokinesis furrow and during pseudopod extension, which requires controlled F-actin polymerization. The molecular players are similar during cytokinesis and phagocytosis, in particular CR3-mediated. Actin filament assembly relies on the two types of actin nucleators, Diaphanous Related-Formins mDia1-3 (DRF) and the Arp2/3 complex, that is activated by actin nucleation promoting factors such as WASP/Wave proteins [15, 16]. The assembly of branched actin filaments by Arp2/3 is stimulated during both FcR and CR3 phagocytosis, while formins are responsible for assembly of linear actin filaments during CR3 phagocytosis [14, 17] and formation of the F-actin ring during cytokinesis [18, 19].

F-actin polymerization is controlled by the Rho family GTPases and phosphoinositides (PIs). Seminal studies by E. Caron showed that the different types of phagocytosis are highly controlled by distinct Rho GTPases. During FcR-mediated phagocytosis, F-actin polymerization is controlled by Cdc42 and Rac [20-22]. Cdc42 activation and phosphatidylinositol-4,5-bisphosphate PI(4,5)P2 accumulation in the nascent phagocytic cup activate N-WASP and the Arp2/3 complex, responsible for pseudopod extension. Rac1 is also essential for F-actin polymerization to complete extension and closure, through activation of the WAVE complex [23]. CR3-mediated uptake requires RhoA activity whose downstream effectors, Rho-Kinase (ROK), the formin mDia1 and myosin II are implicated in polymerization and contraction of F-actin around the particles [14, 17, 20, 21].

Similar to CR3-phagocytosis, RhoA is the key player in F-actin polymerization during cytokinesis furrow ingression and, once activated, controls the recruitment of the formin mDia2, which, together with profilins, triggers the polymerization of unbranched actin filaments [18, 24]. Biosensors of activated, GTP-bound, RhoA indicate that RhoA is activated at a circumferential zone in anaphase and telophase where the furrow contracts [25]. RhoA activation depends on signal delivered by the microtubules of the mitotic spindle, which will be discussed later. Interestingly, while initial studies suggested that RhoA was involved only in CR3 phagocytosis, a recent RNAi screen identified RhoG as a master regulator necessary for both efficient FcR and CR3-mediated phagocytosis [26] and its role has to be analysed further. Whether RhoG is also implicated upstream of RhoA in cytokinesis has not yet been investigated.

Actin dynamics and depolymerization

In addition to polymerization a high turnover of F-actin is also necessary for phagosome closure and successful furrow ingression. PIs present at the plasma membrane and on intracellular membranes are important for actin remodelling and membrane trafficking during phagocytosis and cytokinesis [27, 28]. Most importantly, PI(4,5)P2, which is well known for its role in F-actin remodelling [29], accumulates early during phagosome formation and plays a role in initial F-actin polymerization at the edges of pseudopods to allow their extension [30]. Thereafter, as the phagosome seals, a decrease in PI(4,5)P2 levels contributes to deactivation of Cdc42 and F-actin depolymerization at the base of the cup. PI3 kinase and Phospholipase C are implicated in the reduction of PI(4,5)P2 levels [3]. In addition, the OCRL phosphatase also contributes to PI(4,5)P2 hydrolysis during phagocytosis [31], and during cytokinesis abscission [32]. Severing of actin also relies on the actin regulatory protein cofilin, which catalyses the severing of F-actin thereby providing G-actin subunits to support the rapid turnover of barbed end growth of filaments driving the extension of the plasma membrane. Cofilin is recruited to phagocytic cups and its activity is regulated by LIM kinase that can be activated by the different effectors of Rho GTPases Rac1, Cdc42 and ROK [33]. During cytokinesis, a high rate of actin filament turnover (t1/2 around 30 second) is observed in the ingressing furrow [12], and cofilin is also required for productive furrow contraction [34]. As observed during phagocytosis, PI(4,5)P2 production plays a key role during cytokinesis, by stabilizing the contractile ring after complete ingression [27]. In addition, PI(4,5)P2 hydrolysis from the intercellular bridge is essential for normal abscission in late cytokinesis, by promoting F-actin clearance [32]. PI-regulated polymerization/depolymerization of F-actin is thus both required during phagocytosis and cytokinesis.

Regulation of actin-driven contractility and membrane deformation

The contraction of the actin cytoskeleton during cytokinesis furrow ingression has been extensively studied and myosin II is essential at this step. While engulfment of particles presumably requires contractile forces of myosins, the molecular mechanisms are less clear for phagocytosis. Like in muscle contraction, bipolar filaments (oligomers) of myosin II slide antiparallel actin filaments, resulting in an inward contraction of the ring. Beside these tangential actin filaments at the cell equator, additional actin filaments have been observed that do not align along the furrow but could participate in the contraction via a myosin II-independent mechanism [9, 35]. Rho Kinase promotes myosin II activation by directly phosphorylating the activatory sites on myosin regulatory light chain and by inhibiting the myosin II phosphatase that dephosphorylates those sites [36]. Additional kinases directly activated by RhoA such as Citron kinase and MLCK also contribute to myosin II activation, which drives ring constriction and subsequent ingression of the plasma membrane. Interestingly, reduction of contractibility at the polar cortex is also required for successful furrow ingression [37, 38]. In addition to myosin II activation, actin filaments must be anchored to the plasma membrane for productive furrow ingression. Several proteins linking the plasma membrane to F-actin, such as the ERM (Ezrin/Radixin/Moesin) proteins, Anillin and Septins, likely act in parallel to achieve this [39-42]. Actin filaments also have to be anchored to transduce forces during pseudopods extension; therefore it has to be determined whether these proteins could have an analogous function during phagocytosis. However, ezrin does not play an essential role in phagosome formation but rather during maturation [43], possibly because the architecture and mechanisms of F-actin anchoring are different.

Although several classes of myosin (I, II, V, IX and X) have been detected in the phagocytic cup [44], the underlying mechanisms occurring at the plasma membrane to extend pseudopods, to pull the phagosome inside the cell and close the cup are still unclear. Myosin II localizes in ruffles and early phagocytic cups and is required for both FcR and CR3 phagocytosis [14, 45]. Myosin1G, which binds to both F-actin and phospholipids, could be important for contraction and closure of FcR-dependent phagosomes [46]. Myosin X is recruited to the phagocytic cup and could help pseudopod extension by regulating vesicular trafficking during FcR phagocytosis [47]. Myosin IC is recruited later, suggesting a potential role in phagosome closure, while Myosin V is present on fully internalized phagosomes presumably for maturation and migration of phagosomes [44, 48]. The roles of individual myosins will certainly need more detailed analyses in the future.

Role of microtubules in cytokinesis furrow contraction and phagocytosis

Microtubules play multiple roles in cytokinesis. In contrast, surprisingly little is known about the role of microtubules during phagocytosis. In anaphase, the microtubules of the spindle reorganize to form the central spindle. The central spindle is made of antiparallel bundles of microtubules whose plus ends overlap midway between the spindle poles [49]. Formation of the central spindle requires the bundling factor PRC1, the centralspindlin complex composed of two kinesin MKLP1/ZEN-4/Pavarotti and two MgcRacGAP/Cyk-4/RacGAP50C molecules, and the chromosome passenger complex that includes the Aurora B kinase [4, 5, 49]. The activity of PCR1 and centralspindlin is tightly regulated, so that the central spindle forms and elongates only in anaphase, once the chromosomes have separated. RhoA activation at the equatorial cortex depends on the binding of the cytokinesis Rho GEF (Guanine Nucleotide Exchange Factor) Ect2/Pebble to Cyk-4, coupling the central spindle to furrow ingression [50, 51]. Thus the central spindle and associated molecules control when and where the furrow ingresses by allowing microtubule/actin cross talk. After furrow ingression, the intercellular bridge is filled with a dense array of antiparallel microtubules that overlap in the midbody region and which targets membrane vesicles and serves as a platform for concentrating factors essential for abscission (see below).

During phagocytosis, the organization of microtubules is different compared to cytokinesis, and thus does not likely require the same machinery. For instance, microtubules do not form bundles in the phagocytic cup. Nevertheless, CR3 integrin-mediated phagocytosis, which signals via RhoA, requires functional microtubules [6]. More precisely, the CLIP-170 microtubule plus end protein (+TIP) is targeted to the phagocytic cups and controls the recruitment of the formin mDia1 and thus, optimal F-actin polymerization [52]. These results highlight a microtubule/actin cross talk during CR3-mediated phagocytosis but not FcR-mediated phagocytosis, which should be investigated further taking advantage of the details known for cytokinesis, especially concerning the feedback loop between microtubules and RhoA activation. Indeed, the regulation of RhoA by the Ect2/centralspindlin pathway, once believed to be specific for cytokinesis, now appears to play other functions in cell migration [53] or cell–cell junctions [54].

Membrane Trafficking and Lipid Remodelling During Phagocytosis and Cytokinesis

Focal delivery of vesicles and requirement for membrane trafficking

It has been clearly established that vesicular trafficking is required both for efficient phagosome formation and for successful cytokinesis (Figure 2). The concept of membrane remodelling and ‘focal delivery’ of intracellular compartment at the site of phagocytosis emerged in the late 1990s [55, 56]. Indeed, measurement of the cell surface by flow cytometry or capacitance demonstrated that, instead of diminishing, the cell surface area increases upon phagocytosis [56, 57]. This focal delivery was recently shown to occur at the base of the forming phagosomes and not in extending pseudopods [31]. Membrane delivery could release tension before abscission or phagosome closure, deliver specific cargoes or result in remodelling of the lipid composition [58, 59]. This could also apply to cytokinesis, as reviewed recently [60]. Membrane addition from internal pools to the ingressing furrow has been clearly documented in the case of large cell cytokinesis (e.g. first cell division in Xenopus or sea urchin embryos) [61, 62]. Secretion appears essential for furrow ingression in those cells, likely by furnishing additional cell surface. Systematic genetic studies [63-65] also demonstrated that in small and large cell types, membrane trafficking was essential for intercellular bridge stability and for normal abscission. Confocal and TIRF microscopy also revealed that a number of vesicles from different origins traffic in and out of the bridge after furrow ingression [32, 66-71]. In addition, clear vesicle fusion events to the plasma membrane of the intercellular bridge have been reported [66, 69, 72], indicating that focal delivery is a common feature of cytokinesis as well as phagocytosis.

Figure 2.

Integration of signalling, trafficking and cytoskeleton remodelling during late cytokinesis and phagocytic cup formation. Common regulators are implicated in focal delivery of endosomes during late cytokinesis (A) and late phagocytosis (B), not only to provide membrane surface or tension release but also to target regulatory signaling proteins. Rab proteins such as Rab11 and Rab35, as well as ARF6, contribute to the membrane delivery during both processes. Lipids and notably phosphoinositides play a crucial role in remodeling actin and directing vesicular trafficking. Indeed, hydrolysis of PI(4,5)P2 by OCRL in both processes was recently shown to be important for actin depolymerization. Localization of OCRL depends on vesicle recruitment via Rab35 during late cytokinesis and AP1/Bcl10 during phagocytosis, showing coordinated regulation of signal, actin and vesicular trafficking. Although MT implication have been demonstrated in vesicle delivery during cytokinesis, this is less clear for phagocytosis. While recent studies highlighted a role for ESCRT-III in completion of cytokinesis, the mechanism of phagosome closure has been poorly studied.

Origin of membranes

Although the role of the Golgi apparatus in phagosome formation has been ruled out consensually by several groups [73-75], the role of this organelle and the secretory pathway during cytokinesis has been debated [76, 77]. In large cells, including Drosophila spermatocytes, Caenorhabditis elegans and Xenopus embryos, secretion or Golgi function is required [78-80]. In contrast, small somatic cells do not appear to require secretion, since Brefeldin A (BFA)-treated cells divide normally [71], although a study reported a block in cytokinesis [81]. The local delivery of endosomes does however play an important role in late cytokinesis, as well as in phagosome formation [60, 82]. Evidence for this requirement during cytokinesis and optimal phagocytosis came from studies interfering with the fusion machineries composed of vesicle-soluble N-ethylmaleimide-sensitive factor attachment protein receptors (v-SNAREs) VAMP3 and VAMP7 located on recycling and late endosomes, respectively [83-85], and the plasma membrane t-SNARE syntaxin2 [86]. Whether endocytosis (internalization) is shutdown in metaphase is debated [83, 87]. However, endocytic recycling is halted in metaphase and appears to resume in anaphase/telophase, during furrow ingression and bridge formation [67, 69, 83, 88, 89].

Regulators of membrane trafficking

The regulators of focal exocytosis have begun to be unravelled in recent years both during cytokinesis and phagocytosis. As the Rab family of small GTPases are master controllers of intracellular trafficking [90], it is not a surprise that they are implicated in focal exocytosis and important for successful abscission or efficient phagosome formation. Dominant negative or RNAi approaches showed that Rab11, localized to recycling compartments, is implicated in late events of cytokinesis [67, 78, 91], as well as in phagosome formation [8, 92, 93]. In addition, Rab35, which controls fast recycling, was shown to control post-furrowing cytokinesis events [89, 94]. Rab35 was shown to control the localization of the septin SEPT2 at young intercellular bridges. More recently, Rab35 has been implicated in PI(4,5)P2 hydrolysis and F-actin removal necessary for successful abscission of the daughter cells, through the localization of a pool of the PI(4,5)P2 and PI(3,4,5)P3 phosphatase oculocerebrorenal syndrome of Lowe (OCRL) in late cytokinesis bridges [32]. OCRL is mutated in Lowe syndrome patients [95], and cultured renal cells derived from patients display abscission defects [32]. Of note, mutants in the inositol 5-phosphatase OCRL homolog in Dictyostelium, called Dd5P4, were impaired for phagocytosis of yeast [96]. OCRL was also recently reported to be important for PI(4,5)P2 hydrolysis and scission of prevacuoles containing Yersinia downstream of Rab5 [97] and to restrict the entry of Listeria in non-phagocytic cells [98]. Interestingly, the presence of OCRL at sites of phagocytosis was shown to be important for F-actin depolymerization at the base of the nascent phagosomes and successful phagocytosis. The recruitment of OCRL depends on vesicular recruitment of AP1 and EpsinR adaptors, which is under the control of the NF-kB signalling protein Bcl10 [31]. In addition, a role for Rab35 during phagocytosis was recently highlighted, indicating that Rab35 regulates actin-dependent phagosome formation by recruiting ACAP2, an ARF6 GTPase activating protein [99] or by regulating the localization of Rac1 and Cdc42 [100]. Therefore, Rab35 and/or Rab5 might control PI(4,5)P2 hydrolysis and hence F-actin dynamics via OCRL and ARF6. The small GTP-binding protein ARF6 is indeed a potent regulator of membrane trafficking and F-actin remodelling [101]. ARF6 was shown to be activated during phagosome formation and regulate efficient phagocytosis [73, 75, 102]. Intriguingly, some proteins, which are effectors for both ARF6 and Rab11 GTP-binding proteins, have been implicated in cytokinesis. These include the Rab11-FIP3/4/RIP/RCP (Rab coupling proteins) also named arfophilins, which could play a role to link the activities of Rab11 and ARF6 at the intercellular bridge [72, 103-105]. Therefore, the Rab35/OCRL and the Rab11/FIP3 recycling pathways appear to act in parallel to restrict F-actin accumulation in late intercellular bridges, and are both required for proper cytokinesis abscission [32, 105]. Arfophilins might also play a role during phagosome formation and maturation [93]. In addition, ARF6 could co-ordinate the two recycling pathways regulated by the Rab11 and Rab35 GTPases during cytokinesis and possibly phagocytosis, as activated ARF6 has recently been described to negatively regulate the Rab35 pathway [94].

Role of microtubules in vesicular delivery

The role of the microtubule network in membrane delivery remains to be explored in detail during phagocytosis and cytokinesis. The difficulty resides in designing experimental approaches to question the role of microtubules in traffic without interfering with fundamental effects on the cytoskeleton and cell shape. Earlier studies indicated that treatment of phagocytic cells with microtubules depolymerizing drugs does not interfere with FcR-mediated phagocytosis [6], a result that was confirmed more recently [8, 52]. It is thus tempting to conclude that focal exocytosis, which is required for efficient FcR phagocytosis [58], is independent from microtubules. This, however, should be revisited to directly associate microtubules and vesicle trafficking. During cytokinesis, a role for microtubules in trafficking of vesicles is also difficult to delineate because of the aforementioned reasons. It was however recently highlighted that JIP4 (c-Jun-N-terminal-kinase interacting protein 4), also known as JLP, SPAG9 and SYD1, KIF5B (Kinesin-1) and the dynactin complex control the trafficking of recycling, transferrin-positive, endosomes in and out of the intercellular bridge and are necessary for efficient abscission [70]. Similarly, KIF5B-mediated delivery of Rab11-containing recycling endosomes was proposed to mediate delivery of CR3 receptors and thereby to promote F-actin-rich membrane ruffles during phagocytosis [8]. Recently, the KIF13 kinesin has been found to be involved in the delivery of the PI(3)P-binding protein FYVE-CENT in late cytokinesis bridges, and both proteins are required for normal abscission [106].

Questions and future directions: integration of membrane traffic, signal and cytoskeleton

As discussed already in this review, some players have not so far been implicated in the mechanisms of phagocytosis and cytokinesis. The exocyst complex, a common effector of Rab11 (via the Sec15 subunit) and ARF6 (via Sec10) that controls vesicle docking to the plasma membrane, has been shown to be important for cytokinesis [63-66, 104, 107-109]. Interestingly, subunits of the exocyst complex including Sec10 and Sec15 were found by an RNAi screen in the Drosophila embryonic haemocyte-derived cell line S2 as well as by proteomics on phagosomes [110]. The complex might play a role during phagosome formation as well as during maturation steps, but this has not so far been investigated in detail.

The endosomal sorting complex required for transport (ESCRT) through the ESCRT-III subcomplex, has recently been recognized as essential for abscission [71, 111-115]. This complex is known to drive the budding of HIV viruses from the plasma membrane and of intraluminal vesicles from multivesicular bodies, a process that has been reconstituted in vitro [116]. Given the topology of membrane bending, with ESCRT driving inward membrane bending while the pseudopods extend as membrane folds that eventually fuse, it is unlikely that the ESCRT machinery also plays a role in phagosome closure but this should be investigated.

The septins are a highly conserved family of filamentous GTPases that control bud site selection in Saccharomyces cerevisiae and were shown to be important players in cytokinesis of mammalian cells [42, 117]. SEPT2 and SEPT11 were also reported to play a role in phagocytosis [118], but their precise roles and connections with the actin cytoskeleton are not elucidated.

Finally, the GTP-binding protein Dynamin has well-established activity in fission reactions at the plasma membrane and on internal compartments, but its role both in cytokinesis and in phagocytosis is ill defined. Dynamin 2 is enriched in the phagocytic cup [119], and it has also been reported to be present in the intercellular bridge [120]. Although interfering with its presence or function impairs both phagocytosis and cytokinesis [119, 120], it is unclear whether Dynamin acts as a mechanical ‘pinchase’, or promotes vesicle formation and scission on internal compartments and hence provides membranes for focal exocytosis [121, 122], or co-ordinates F-actin remodelling. The role of Dynamin should therefore be revisited here.

In conclusion, emerging evidence indicate that, during cytokinesis as well as phagocytosis, vesicle recruitment might act to serve as platforms of signalling activity, in particular regulating F-actin polymerization/depolymerization, and may modify the local membrane composition. The contribution of lipids such as PIs or phosphatidic acid in organizing domains in the membranes could be a mean to recruit regulators and assist in the completion of phagosome formation. There is no doubt that the ‘ménage à trois’, that takes place between vesicles, signal and actin during phagocytosis and cytokinesis might also play a prominent role during other cell functions, such as migration or synapse formation; phagosome formation and cytokinesis can be considered as some of the archetypes of complex cell functions.


We thank Dr Mark Scott for reading the manuscript and Dr Laurent Chesneau for the fluorescent image. Work in the laboratory of FN was supported by grants from the Fondation pour la Recherche Médicale (FRM, INE20041102865), CNRS (ATIP Program), Ville de Paris and Agence Nationale de la Recherche (2011 BSV3 025 02). Work in the laboratory of A. E. was supported by grants from Institut Pasteur, the CNRS, the Schlumberger Foundation for Education and Research, the Fondation pour la Recherche Médicale (FRM DEQ20120323707) and the Association pour la Recherche sur le Cancer (ARC). C. D. was supported by post-doctoral fellowships from CNRS and ANRS.