Sar1

Sar1 is a small GTPase belonging to the Ras superfamily that regulates the formation of COPII-coated vesicles at endoplasmic reticulum (ER) exit sites. In its GDP-bound form, Sar1 is predominantly cytosolic. The ER membrane–localized guanine nucleotide exchange factor Sec12 promotes GDP-to-GTP exchange, generating Sar1-GTP. This nucleotide-bound form exposes an N-terminal amphipathic helix that inserts into the ER membrane, anchoring Sar1 and helping to bend the membrane at ER exit sites.

Membrane-anchored Sar1-GTP recruits the inner COPII coat composed of Sec23 and Sec24, which selects cargo. This is followed by assembly of the outer coat Sec13/Sec31, driving vesicle budding. After vesicle formation, intrinsic GTPase activity of Sar1, stimulated by Sec23, hydrolyzes GTP to GDP, triggering coat disassembly and uncoating of the vesicle, allowing fusion with the Golgi apparatus.

Two Sar1 paralogs exist in many vertebrates: SAR1A and SAR1B. In yeast, the gene is SAR1p. While functionally conserved, vertebrate paralogs show differences in tissue expression and cargo handling; SAR1B, for example, has a notable role in intestinal chylomicron assembly and secretion.

Sar1 is essential for ER-to-Golgi transport and overall secretory pathway function. Its activity is tightly regulated at ER exit sites and integrates signals from cargo load and coat assembly dynamics. Disruption of Sar1 function impairs cargo trafficking and can lead to accumulation of proteins in the ER.