GTPaseSar1

GTPase Sar1, also known as SAR1A, is a small GTPase protein that plays a crucial role in the early secretory pathway of eukaryotic cells. It is a key regulator of COPII vesicle formation, which is the primary mechanism for transport of proteins from the endoplasmic reticulum (ER) to the Golgi apparatus. Sar1 exists in two nucleotide-bound states: GDP-bound (inactive) and GTP-bound (active). The transition between these states is mediated by guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs).

The activation of Sar1 is initiated when it binds to the ER membrane. This binding is facilitated by a GEF called Sec12. Upon recruitment to the membrane, Sar1 undergoes a conformational change, releasing GDP and binding GTP. This GTP-bound Sar1 then recruits other components of the COPII coat, such as Sec23 and Sec24, to the ER membrane. These proteins, along with Sec13 and Sec31, form the COPII coat that buds off from the ER, encapsulating cargo proteins within a vesicle.

The GTPase activity of Sar1 is eventually stimulated by a GAP, which promotes the hydrolysis of GTP to GDP. This hydrolysis leads to the dissociation of Sar1 from the COPII coat, allowing the vesicle to uncoat and fuse with its target compartment, typically the Golgi. Dysregulation of Sar1 function can lead to impaired ER-to-Golgi transport, affecting protein secretion and cellular homeostasis. Mutations in SAR1A have been linked to certain human diseases, highlighting its importance in cellular processes.