GBF1

GBF1, or Golgi brefeldin A resistance factor 1, is a large guanine nucleotide exchange factor (GEF) belonging to the Sec7 family that activates ARF small GTPases, primarily ARF1. By catalyzing the exchange of GDP for GTP on ARF1, GBF1 promotes recruitment of COPI coatomer complexes to Golgi membranes, facilitating vesicle formation and trafficking between the endoplasmic reticulum and the Golgi, as well as within Golgi compartments. It is essential for maintaining Golgi structure and the efficiency of the secretory pathway in many cell types.

GBF1 is a modular, peripheral membrane protein enriched at the cis-Golgi and ER‑Golgi intermediate compartments. It contains a catalytic Sec7 domain responsible for ARF activation and regulatory regions that control membrane association and substrate specificity, including C-terminal regulatory motifs. Localization and activity are influenced by lipid interactions, such as phosphatidylinositol 4-phosphate, and by interacting proteins. GBF1 activity can be inhibited by small molecules, notably brefeldin A (BFA) and golgicide A (GCA), which bind GBF1 and block ARF activation, causing Golgi disassembly and redistribution of Golgi enzymes to the endoplasmic reticulum.

In addition to its fundamental role in cellular trafficking, GBF1 is exploited by certain viruses to remodel host membranes for replication organelles; consequently, GBF1 inhibitors can suppress replication of some positive-sense RNA viruses. In normal physiology, GBF1 supports efficient protein processing and secretion, and its function is a key component of Golgi maintenance and vesicular trafficking.