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PMID: 17804820 Published · ppublish English Journal Article Research Support, N.I.H., Intramural Research Support, Non-U.S. Gov't

ARL4D recruits cytohesin-2/ARNO to modulate actin remodeling.

Molecular biology of the cell ·Vol. 18 ·No. 11 ·2007-11-00 ·Pages 4420-37

Li CC, Chiang TC, Wu TS, Pacheco-Rodriguez G, Moss J, Lee FJ

Abstract

ARL4D is a developmentally regulated member of the ADP-ribosylation factor/ARF-like protein (ARF/ARL) family of Ras-related GTPases. Although the primary structure of ARL4D is very similar to that of other ARF/ARL molecules, its function remains unclear. Cytohesin-2/ARF nucleotide-binding-site opener (ARNO) is a guanine nucleotide-exchange factor (GEF) for ARF, and, at the plasma membrane, it can activate ARF6 to regulate actin reorganization and membrane ruffling. We show here that ARL4D interacts with the C-terminal pleckstrin homology (PH) and polybasic c domains of cytohesin-2/ARNO in a GTP-dependent manner. Localization of ARL4D at the plasma membrane is GTP- and N-terminal myristoylation-dependent. ARL4D(Q80L), a putative active form of ARL4D, induced accumulation of cytohesin-2/ARNO at the plasma membrane. Consistent with a known action of cytohesin-2/ARNO, ARL4D(Q80L) increased GTP-bound ARF6 and induced disassembly of actin stress fibers. Expression of inactive cytohesin-2/ARNO(E156K) or small interfering RNA knockdown of cytohesin-2/ARNO blocked ARL4D-mediated disassembly of actin stress fibers. Similar to the results with cytohesin-2/ARNO or ARF6, reduction of ARL4D suppressed cell migration activity. Furthermore, ARL4D-induced translocation of cytohesin-2/ARNO did not require phosphoinositide 3-kinase activation. Together, these data demonstrate that ARL4D acts as a novel upstream regulator of cytohesin-2/ARNO to promote ARF6 activation and modulate actin remodeling.

MeSH Terms
ADP-Ribosylation Factors/genetics,metabolism Actins/metabolism Animals Catalysis Cell Line Cell Membrane/metabolism Cell Movement Chlorocebus aethiops GTPase-Activating Proteins/metabolism Guanosine Triphosphate/metabolism Humans Membrane Proteins/genetics,metabolism Mutation/genetics Phosphatidylinositol 3-Kinases/metabolism Protein Binding Protein Transport Proto-Oncogene Proteins c-akt/metabolism Signal Transduction Transcription Factors/metabolism
Chemicals
Actins GTPase-Activating Proteins Membrane Proteins Transcription Factors cytohesin-2 Guanosine Triphosphate Proto-Oncogene Proteins c-akt ADP-ribosylation factor related proteins ADP-Ribosylation Factors
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Li Chun-Chun
Institute of Molecular Medicine, College of Medicine, National Taiwan University, Taipei 100, Taiwan.
Chiang Tsai-Chen
Wu Tsung-Sheng
Pacheco-Rodriguez Gustavo
Moss Joel
Lee Fang-Jen S
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Article Info
Journal
Molecular biology of the cell
Abbr.
Mol Biol Cell
ISSN
1059-1524
DOI
10.1091/mbc.e07-02-0149
Published
2007-11-00
Epub
2007-00-05
Pages
4420-37
Language
English
Region
United States
NLM ID
9201390
PMCID
PMC2043562
Subset
IM
Grants
Intramural NIH HHS · United States
External Links
PubMed source DOI: 10.1091/mbc.e07-02-0149 PMC Full Text View journal details
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