ARF proteins: roles in membrane traffic and beyond

Abstract

The ADP-ribosylation factor (ARF) small GTPases regulate vesicular traffic and organelle structure by recruiting coat proteins, regulating phospholipid metabolism and modulating the structure of actin at membrane surfaces. Recent advances in our understanding of the signalling pathways that are regulated by ARF1 and ARF6, two of the best characterized ARF proteins, provide a molecular context for ARF protein function in fundamental biological processes, such as secretion, endocytosis, phagocytosis, cytokinesis, cell adhesion and tumour-cell invasion.

Regulation of actin cytoskeleton dynamics by Arf-family GTPases

“…including phagocytosis, some forms of endocytosis, cell adhesion, migration, invasion of the extracellular matrix. and neurite outgrowth [2]. In a similar fashion to Arf1, Arf6 can activate both phospholipase D and type I PIP5 kinases, but it does so at the plasma membrane and on endosomal compartments [6].…”

“…The ADP-ribosylation factor (Arf) proteins are small, ubiquitously expressed GTP-binding proteins best known for their role in membrane trafficking [2]. The six mammalian Arfs are divided into three classes on the basis of sequence relatedness, with class I containing Arf1, Arf2 and Arf3, class II containing Arf4 and Arf5, and class III containing only Arf6.…”

“…For class I and class II Arfs, these complexes include multimeric coat protein complexes such as COPI (coat protein complex I), AP-1 (adaptor protein complex 1), AP-3 and AP-4, in addition to monomeric adaptors of the GGA (Golgi-associated, gamma adaptin ear-containing and Arf binding) and Mint (Munc18-interacting protein) families [2]. These vesicle coats serve to concentrate cargo proteins in the plane of the membrane and might help to deform the membrane surface, thereby facilitating the formation of carrier vesicles.…”

Specificity of Arl2/Arl3 signaling is mediated by a ternary Arl3‐effector‐GAP complex

“…The ADP-ribosylation factor (Arf) subfamily belongs to the superfamily of Ras-related GTP-binding proteins (G proteins) and contains several members (Arf1-6, Sar1) which regulate membrane traffic [1]. The 19 currently known, less characterized Arf-like (Arl) proteins form a heterogeneous group of proteins with less sequence homology to each other and do not serve as cofactors in the ADP-ribosylation reaction of Ga proteins [2,3], but do share similar structural features with Arf proteins [4].…”

Arf6 regulates tumour angiogenesis and growth through HGF-induced endothelial β1 integrin recycling

“…The small GTPase Arf6 plays important roles in cell migration and membrane dynamics by regulating intracellular membrane trafficking and reorganizing the actin cytoskeleton 17,18 . Arf6 cycles through a GDP-bound inactive and a GTP-bound active form.…”