ARF6

ADP-ribosylation factor 6 (ARF6) is a small guanine nucleotide-binding protein belonging to the ARF family, which plays a critical role in intracellular vesicle trafficking and membrane dynamics. Like other ARFs, ARF6 cycles between an inactive GDP-bound state and an active GTP-bound state, regulated by guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs). This cycling enables ARF6 to mediate the recruitment of effector proteins to specific cellular membranes, facilitating processes such as endocytosis, exocytosis, and organelle biogenesis.

ARF6 is predominantly localized to the plasma membrane and recycling endosomes, where it influences the formation and movement of vesicles. Its activity is essential for maintaining cellular polarity, particularly in epithelial cells, where it helps regulate the positioning of proteins and lipids in apical and basolateral domains. Dysregulation of ARF6 has been implicated in various pathological conditions, including cancer progression, where it contributes to cell migration, invasion, and metastasis by altering cytoskeletal dynamics and membrane trafficking.

Structurally, ARF6 shares conserved features with other ARF proteins, including a myristoylation site at its N-terminus, which anchors it to membranes. Mutations or post-translational modifications affecting ARF6 function can disrupt normal cellular processes, leading to disease. Research on ARF6 continues to explore its potential as a therapeutic target, particularly in oncology and neurodegenerative disorders, where its aberrant activity may drive disease progression.