A positive signal prevents secretory membrane cargo from recycling between the Golgi and the ER

Authors

  • Matteo Fossati,

    1. BIOMETRA Department, CNR Institute of Neuroscience, Università degli Studi di Milano, Milano, Italy
    Current affiliation:
    1. Institute of Biology at the École Normale Supérieure (IBENS), Paris, France
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  • Sara F Colombo,

    1. BIOMETRA Department, CNR Institute of Neuroscience, Università degli Studi di Milano, Milano, Italy
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  • Nica Borgese

    Corresponding author
    1. BIOMETRA Department, CNR Institute of Neuroscience, Università degli Studi di Milano, Milano, Italy
    2. Department of Health Science, Magna Graecia University of Catanzaro, Catanzaro, Italy
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Abstract

The Golgi complex and ER are dynamically connected by anterograde and retrograde trafficking pathways. To what extent and by what mechanism outward-bound cargo proteins escape retrograde trafficking has been poorly investigated. Here, we analysed the behaviour of several membrane proteins at the ER/Golgi interface in live cells. When Golgi-to-plasma membrane transport was blocked, vesicular stomatitis virus glycoprotein (VSVG), which bears an ER export signal, accumulated in the Golgi, whereas an export signal-deleted version of VSVG attained a steady state determined by the balance of retrograde and anterograde traffic. A similar behaviour was displayed by EGF receptor and by a model tail-anchored protein, whose retrograde traffic was slowed by addition of VSVG's export signal. Retrograde trafficking was energy- and Rab6-dependent, and Rab6 inhibition accelerated signal-deleted VSVG's transport to the cell surface. Our results extend the dynamic bi-directional relationship between the Golgi and ER to include surface-directed proteins, uncover an unanticipated role for export signals at the Golgi complex, and identify recycling as a novel factor that regulates cargo transport out of the early secretory pathway.

Synopsis

image

Plasma membrane (PM)-targeted proteins cycle back and forth between ER and Golgi. Proteins equipped with a polypeptide export signature escape the Rab6-regulated retrograde pathway more easily, reaching the PM faster.

  • Correctly folded membrane proteins destined to the plasma membrane may engage in recycling between the Golgi and the ER during their transport through the early secretory pathway.
  • Vesicular Stomatitis Virus Glycoprotein is prevented from entering the Golgi-to-ER recycling pathway due to the presence of a tyrosine and diacidic-based ER export signal in its cytosolic tail.
  • The small GTPase Rab6 is required for the retrograde transport of signal-deficient, surface-directed cargo proteins.
  • Recycling of membrane cargoes within the early secretory pathway is a novel mechanism regulating the overall transport rate through the secretory pathway.

Ancillary