Rab6-mediated retrograde trafficking from the Golgi: the trouble with tubules

ABSTRACT

Next year marks one-quarter of a century since the discovery of the so-called COPI-independent pathway, which operates between the Golgi apparatus and the endoplasmic reticulum (ER) in eukaryotic cells. Unlike almost all other intracellular trafficking pathways, this pathway is not regulated by the physical accumulation of multisubunit proteinaceous coat molecules, but instead by the small GTPase Rab6. What also sets it apart from other pathways is that the transport carriers themselves often take the form of tubules, rather than conventional vesicles. In this review, we assess the relevant literature that has accumulated to date, in an attempt to provide a concerted description of how this pathway is regulated. We discuss the possible cargo molecules that are carried in this pathway, and the likely mechanism of Rab6 tubule biogenesis, including how the cargo itself may play a critical role. We also provide perspective surrounding the various molecular motors of the kinesin, myosin and dynein families that have been implicated in driving Rab6-coated tubular membranes long distances through the cell prior to delivering their cargo to the ER. Finally, we also raise several important questions that require resolution, if we are to ultimately provide a comprehensive molecular description of how the COPI-independent pathway is controlled.

KEYWORDS:

• membrane traffic
• retrograde transport
• Rab6
• Golgi apparatus
• membrane tubules
• COPI-independent transport

Acknowledgments

The authors gratefully acknowledge all the members of the Cell Screening Laboratory for comments on this article. Work at the Cell Screening Laboratory is funded by the UCD College of Science. L.G.D. is supported by a Government of Ireland Postgraduate Scholarship from the Irish Research Council (IRC), under grant [GOIPG/2022/1944]. The figures were created with BioRender.com.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

The work was supported by the Irish Research Council [GOIPG/2022/1944].