Rab6

Rab6 refers to a subgroup of the Rab family of small GTPases that regulate membrane traffic in eukaryotic cells. In humans, the Rab6 family includes Rab6A (which also gives rise to an isoform known as Rab6A′ through alternative initiation) and Rab6B. These proteins are predominantly localized to the Golgi apparatus and associated transport carriers, where they cycle between an active GTP-bound state and an inactive GDP-bound state to coordinate vesicle budding, movement, and tethering.

Rab6 plays a central role in Golgi-to-ER retrograde transport and in intra-Golgi trafficking. It governs the formation and targeting of vesicles that retrieve Golgi resident enzymes and other cargo back toward the endoplasmic reticulum, as well as trafficking events within Golgi compartments. Rab6 exerts its effects by engaging a set of effector proteins that mediate motor activity, tethering, and SNARE-mediated fusion, thereby influencing vesicle movement along microtubules and docking at appropriate membranes.

Biochemically, Rab6 proteins are anchored to membranes via post-translational prenylation at a C-terminal motif, typically CC or CXC, which allows association with Golgi membranes and vesicles. The activity of Rab6 is governed by guanine nucleotide exchange factors (GEFs) that activate it and GTPase-activating proteins (GAPs) that inactivate it, ensuring proper timing and location of trafficking events.

Beyond vesicle transport, Rab6 contributes to the maintenance of Golgi structure and cargo sorting. Alterations in Rab6-regulated trafficking can affect secretion and glycoprotein processing, and Rab6 function has been examined in various biological contexts, including development, cell polarity, and disease settings where secretory pathway efficiency is important.