Structure and function analysis of the CMS/CIN85 protein family identifies actin-bundling properties and heterotypic-complex formation.
Members of the CMS/CIN85 protein family participate in clathrin-mediated endocytosis and play a crucial role in maintaining the kidney filtration barrier. The CMS protein structure includes three Src homology 3 (SH3) domains and a proline-rich (PR) region that is connected by a 'linker' sequence to a coiled-coil (CC) domain. We show that CMS is a component of special actin-rich adhesion structures--podosomes--and demonstrate specific actin-binding properties of CMS. We have found that the entire C-terminal half of CMS is necessary for efficient binding to filamentous actin (F-actin). CMS and CIN85 can crosslink F-actin into bundles, a function that depends on the PR region and the CC domain. Removal of these domains reduces migration. CMS can also form heterotypic complexes with CIN85. CIN85 is expressed as multiple isoforms that share the CC domain, suggesting that heterotypic interactions with CMS provides a mechanism to regulate CMS binding to F-actin and thus for modulating dynamic rearrangements of the cytoskeleton.
Gaidos
Gabriel
G
Department of Biochemistry, Boston University School of Medicine, 715 Albany Street, Boston, MA 02118, USA.
Soni
Shefali
S
Oswald
Duane J
DJ
Toselli
Paul A
PA
Kirsch
Kathrin H
KH
D000199:Actins / Q000302:isolation & purification / Q000378:metabolism*; D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D002465:Cell Movement; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D003599:Cytoskeleton / Q000378:metabolism; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D041681:NIH 3T3 Cells; D050199:Podocytes / Q000166:cytology / Q000378:metabolism*; D018909:src Homology Domains / Q000235:genetics / Q000502:physiology
D000199:Actins; D048868:Adaptor Proteins, Signal Transducing; C114545:CD2-associated protein; D003598:Cytoskeletal Proteins; C433810:SH3KBP1 protein, human