Rab8As

Rab8As refers to Rab8A-like proteins, a subset of the Rab family of small GTPases that regulate vesicular trafficking in eukaryotic cells. In humans and other vertebrates, Rab8A and Rab8B are the main paralogs, and they share substantial sequence similarity and overlapping roles in membrane transport and cell polarity.

Gene and protein features define Rab8A family members. The proteins are small GTPases that act as molecular switches, cycling between an inactive GDP-bound state and an active GTP-bound state. They are typically expressed in many tissues, with Rab8A and Rab8B encoded by separate genes (RAB8A and RAB8B in humans). The activity of Rab8A proteins is controlled by guanine nucleotide exchange factors (GEFs) such as Rabin8, which promote the active GTP-bound form, and by GTPase-activating proteins (GAPs) that stimulate hydrolysis to the GDP-bound form.

Cellular functions encompass several trafficking pathways. Rab8A proteins participate in trafficking from the trans-Golgi network to the plasma membrane and contribute to basolateral sorting in polarized epithelial cells. They are also involved in ciliogenesis and ciliary membrane trafficking, where they coordinate cargo delivery to the cilium. Rab8A interacts with multiple effectors, including components of the exocyst complex and cytoskeletal regulators, to promote vesicle docking, fusion, and cytoskeletal remodeling. Their activity is often coordinated with other Rab GTPases, such as Rab11, during recycling and delivery routes.

Evolution and terminology note that Rab8A-like proteins are conserved across many eukaryotes, with distinct paralogs in some lineages. In yeast, a Rab8 homolog is present but named differently (for example, Ypt8). Clinically, dysregulation of Rab8A pathways can impact ciliary function and epithelial cell polarity, with potential implications for diseases involving trafficking defects, though the specifics can vary by organism and tissue context.