ADP-ribosylation factors (ARFs) and ARF-like 1 (ARL1) have both specific and shared effectors: characterizing ARL1-binding proteins.
Despite the 40-60% identity between ADP-ribosylation factors (ARFs) and ARF-like (ARL) proteins, distinct functional roles have been inferred from findings that ARLs lack the biochemical or genetic activities characteristic of ARFs. The potential for functional overlap between ARFs and ARLs was examined by comparing effects of expression on intact cells and the ability to bind effectors. Expression of [Q71L]ARL1 in mammalian cells led to altered Golgi structure similar to, but less dramatic than, that reported previously for [Q71L]ARF1. Two previously identified partners of ARFs, MKLP1 and Arfaptin2/POR1, also bind ARL1 but not ARL2 or ARL3. Two-hybrid screens of human cDNA libraries with dominant active mutants of human ARL1, ARL2, and ARL3 identified eight different but overlapping sets of binding partners. Specific interactions between ARL1 and two binding proteins, SCOCO and Golgin-245, are defined and characterized in more detail. Like ARFs and ARL1, the binding of SCOCO to Golgi membranes is rapidly reversed by brefeldin A, suggesting the presence of a brefeldin A-sensitive ARL1 exchange factor. These data reveal a complex network of interactions between GTPases in the ARF family and their effectors and reveal a potential for cross-talk not demonstrated previously.
Van Valkenburgh
H
H
Department of Biochemistry, Emory University School of Medicine, Atlanta, Georgia 30322-3050, USA.
Shern
J F
JF
Sharer
J D
JD
Zhu
X
X
Kahn
R A
RA
D020727:ADP-Ribosylation Factors / Q000302:isolation & purification / Q000378:metabolism*; D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D001324:Autoantigens / Q000378:metabolism; D001483:Base Sequence; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D002846:Chromatography, Affinity; D005136:Eye Proteins / Q000378:metabolism; D006056:Golgi Apparatus / Q000378:metabolism / Q000648:ultrastructure; D007150:Immunohistochemistry; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D026901:Membrane Transport Proteins; D008854:Microscopy, Electron; D008969:Molecular Sequence Data; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism; D011485:Protein Binding; D011994:Recombinant Proteins / Q000302:isolation & purification / Q000378:metabolism; D014157:Transcription Factors; D020798:Two-Hybrid System Techniques
C485676:ARL2BP protein, human; D048868:Adaptor Proteins, Signal Transducing; C121938:Arl2bp protein, mouse; D001324:Autoantigens; D002352:Carrier Proteins; D005136:Eye Proteins; C098772:GOLGA4 protein, human; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D011994:Recombinant Proteins; C430910:SCOC protein, human; D014157:Transcription Factors; C098032:UNC119 protein, human; D010727:Phosphoric Diester Hydrolases; C097313:ADP-ribosylation factor related proteins; D020727:ADP-Ribosylation Factors