A positive signal prevents secretory membrane cargo from recycling between the Golgi and the ER
Article first published online: 25 JUL 2014
© 2014 The Authors
The EMBO Journal
Volume 33, Issue 18, pages 2080–2097, 17 September 2014
How to Cite
The EMBO Journal (2014) 33: 2080–2097
- Issue published online: 17 SEP 2014
- Article first published online: 25 JUL 2014
- Manuscript Accepted: 25 JUN 2014
- Manuscript Revised: 17 JUN 2014
- Manuscript Received: 2 MAR 2014
- Investigator Grant 2009
- Italian Association for Cancer Research (AIRC)
- CNR Research Project on Aging
- Regione Lombardia Project MbMM-convenzione . Grant Number: 18099/RCC
- University of Milan
- live cell imaging;
- retrograde transport;
- secretory pathway;
- VSV glycoprotein
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.
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.