Rab1

Rab1 is a small GTPase of the Rab family that regulates vesicular trafficking along the early secretory pathway. In humans, two paralogs, Rab1A and Rab1B, are encoded by the RAB1A and RAB1B genes. Rab1 proteins localize primarily to the endoplasmic reticulum (ER) and the ER-Golgi intermediate compartment (ERGIC), with a presence at the cis-Golgi, consistent with a role in ER-to-Golgi transport.

Function and mechanism: Rab1 cycles between an inactive GDP-bound state and an active GTP-bound state. In its GTP-bound form, Rab1 engages a set of effector proteins that mediate vesicle budding, tethering, docking, and ultimately SNARE-mediated fusion with the Golgi. Activation is driven by guanine nucleotide exchange factors (GEFs), notably components of the TRAPP complex, while GDP-bound Rab1 is extracted from membranes by GDIs, and GTP hydrolysis is accelerated by GTPase-activating proteins (GAPs).

Localization and interactions: Rab1 acts at ER-to-Golgi trafficking, influencing the formation and targeting of COPII-derived vesicles at ER exit sites and the subsequent tethering of vesicles at ERGIC and the cis-Golgi. Tethering/docking factors such as p115, GM130, and Golgin-84 function as Rab1 effectors, coordinating membrane juxtaposition and fusion.

Isoforms and clinical relevance: Rab1A and Rab1B have overlapping functions but may differ in tissue expression. Rab1A is often upregulated in cancer and linked to changes in secretory capacity, whereas Rab1B supports general ER-Golgi trafficking across cell types. Disruption of Rab1 activity can cause Golgi fragmentation and ER stress. Rab1 can be hijacked by pathogens; for example, Legionella pneumophila effectors DrrA/SidM modify Rab1 to modulate host trafficking during infection.

In model organisms, Rab1 corresponds to yeast Ypt1, reflecting a conserved role in ER-to-Golgi transport.