ARNO through Its Coiled-coil Domain Regulates Endocytosis at the Apical Surface of Polarized Epithelial Cells

ARNO is a guanine-nucleotide exchange protein for the ARF family of GTPases. Here we show that in polarized epithelial cells, ARNO is localized exclusively to the apical plasma membrane, where it regulates endocytosis. Expression of ARNO stimulates apical endocytosis of the polymeric immunoglobulin...

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Bibliographic Details
Published in:The Journal of biological chemistry 2006-05, Vol.281 (19), p.13300-13308
Main Authors: Shmuel, Miriam, Santy, Lorraine C., Frank, Scott, Avrahami, Dana, Casanova, James E., Altschuler, Yoram
Format: Article
Language:English
Subjects:
ADP-Ribosylation Factors - genetics
ADP-Ribosylation Factors - metabolism
Animals
Cell Line
Cell Membrane - metabolism
Dogs
Endocytosis - physiology
Epithelial Cells - cytology
Epithelial Cells - metabolism
Gene Expression Regulation
GTPase-Activating Proteins - genetics
GTPase-Activating Proteins - metabolism
Humans
Protein Structure, Tertiary
Protein Transport
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Summary:ARNO is a guanine-nucleotide exchange protein for the ARF family of GTPases. Here we show that in polarized epithelial cells, ARNO is localized exclusively to the apical plasma membrane, where it regulates endocytosis. Expression of ARNO stimulates apical endocytosis of the polymeric immunoglobulin receptor, and coexpression of ARF6 with ARNO leads to a synergistic stimulation of apical endocytosis. Expression of a dominant negative ARF6 mutant, ARF6-T27N, antagonizes this stimulatory effect. Deletion of the N-terminal coiled-coil (CC) domain of ARNO causes the mutant ARNO to localize to both the apical and basolateral plasma membranes. Expression of the CC domain alone abolishes ARNO-induced apical endocytosis as well as co-localization of IgA-receptor complexes with ARNO and clathrin. These results suggest that the CC domain contributes to the specificity of apical localization of ARNO through association with components of the apical plasma membrane. We conclude that ARNO acts together with ARF6 to regulate apical endocytosis.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M513723200