RAB8A

Rab8A is a member of the Rab family of small GTPases that regulate vesicular trafficking in eukaryotic cells. In humans it is encoded by the RAB8A gene, and it has a closely related paralog, Rab8B. Rab8A proteins cycle between an inactive GDP-bound state in the cytosol and an active GTP-bound state associated with membranes. The cycling is controlled by guanine nucleotide exchange factors that promote GTP loading and by GTPase-activating proteins that stimulate hydrolysis. A key activator of Rab8A in many pathways is Rabin8, which promotes its activation at sites such as the base of cilia and the trans-Golgi network.

Functionally, Rab8A governs vesicle trafficking from the trans-Golgi network and recycling endosomes to the plasma membrane, contributing to polarized delivery of cargo in epithelial cells. It also plays a pivotal role in ciliogenesis, supporting the trafficking of membrane components to the ciliary membrane and facilitating cilium assembly in several cell types. Rab8A operates with other Rab proteins and cytoskeletal motors to coordinate vesicle docking and fusion to appropriate membrane domains.

Rab8A is post-translationally modified at its C-terminus by prenylation, a modification that promotes membrane association essential for its activity. Its effectors mediate downstream steps in vesicle targeting, docking, and fusion, linking Rab8A signaling to broader exocytic and ciliogenic trafficking pathways.

Disruptions in Rab8A-regulated trafficking can affect epithelial polarity and ciliogenesis, highlighting Rab8A’s role in basic cellular organization and development.