TY - JOUR
AU - Chavrier, Philippe
AB - 


The unique cellular distribution of individual ADP-ribosylation factor (ARF) proteins and the molecules with which they interact are vital in dictating ARF-protein function. The mutually exclusive properties in cellular distribution and function of mammalian ARF1 and ARF6 have been extensively investigated. However, parallels in the cellular roles of both these ARF proteins in vesicle budding and actin remodelling is becoming increasingly evident.


ARF1–GTP drives COPI-mediated vesicle budding along the biosynthetic and secretory pathway. ARF1 also regulates the formation of clathrin-coated vesicles at the trans-Golgi network by promoting the recruitment of adaptor-protein complexes AP-1, AP-3, AP-4, and the GGAs from the cytosol onto membranes. ARF1 activation has been shown to stimulate the assembly of spectrin and the actin cytoskeleton on Golgi membranes.


Nucleotide exchange on ARF is regulated by the Sec7-domain-containing GEFs. Site-specific targeting of GBF- and BIG-family GEFs to Golgi subcompartments might have a prominent role in the formation of coats at specific locations. Membrane lipid composition and temporal aspects of vesicle budding can affect the targeting of ARF1 to Golgi membranes.


GTP hydrolysis on ARF1 is required for the dissociation of coat proteins from transport vesicles, and is mediated by a family of ARF GAPs. GTP-hydrolysis on ARF1 is also required for cargo packaging, and ARF GAPs might function to couple cargo sorting with vesicle formation.


ARF6 localizes to the plasma membrane and endosomal compartments, in which it regulates clathrin-dependent endocytic membrane trafficking, as well as the trafficking and sorting of molecules that lack cytoplasmic AP-2 and clathrin sorting sequences, through a unique endocytic route. ARF6 has also been implicated in actin remodelling at the cell periphery. The effects of ARF6 on the actin cytoskeleton are thought to occur through the activation of the Rac1 GTPase and/or its effect on phopholipid metabolism.


The ARF6-GTPase cycle can impinge on several cellular events that require rapid changes in cell-surface morphology and as such, directly impinges on cellular processes such as phagocytosis, cell–cell adhesion, cell migration, tumour-cell invasion and cytokinesis.



TI - ARF proteins: roles in membrane traffic and beyond
JF - Nature Reviews Molecular Cell Biology
DO - 10.1038/nrm1910
DA - 2006-05-01
UR - https://www.deepdyve.com/lp/springer-journals/arf-proteins-roles-in-membrane-traffic-and-beyond-T2fCLc7X4q
SP - 347
EP - 358
VL - 7
IS - 5
DP - DeepDyve
ER -