Mammalian Fat1 cadherin regulates actin dynamics and cell-cell contact.
Fat cadherins form a distinct subfamily of the cadherin gene superfamily, and are featured by their unusually large extracellular domain. In this work, we investigated the function of a mammalian Fat cadherin. Fat1 was localized at filopodial tips, lamellipodial edges, and cell-cell boundaries, overlapping with dynamic actin structures. RNA interference-mediated knockdown of Fat1 resulted in disorganization of cell junction-associated F-actin and other actin fibers/cables, disturbance of cell-cell contacts, and also inhibition of cell polarity formation at wound margins. Furthermore, we identified Ena/vasodilator-stimulated phosphoproteins as a potential downstream effector of Fat1. These results suggest that Fat1 regulates actin cytoskeletal organization at cell peripheries, thereby modulating cell contacts and polarity.
Tanoue
Takuji
T
RIKEN Center for Developmental Biology, Minatojima-Minamimachi, Chuo-ku, Kobe 650-0047, Japan.
Takeichi
Masatoshi
M
D008841:Actin Cytoskeleton / Q000378:metabolism / Q000648:ultrastructure; D000199:Actins / Q000378:metabolism*; D000818:Animals; D001665:Binding Sites / Q000235:genetics; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D002448:Cell Adhesion / Q000235:genetics*; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D016764:Cell Polarity / Q000235:genetics*; D005333:Fetus; D006801:Humans; D007365:Intercellular Junctions / Q000378:metabolism / Q000648:ultrastructure; D051379:Mice; D011485:Protein Binding / Q000235:genetics; D017434:Protein Structure, Tertiary / Q000235:genetics; D011554:Pseudopodia / Q000378:metabolism* / Q000648:ultrastructure; D014945:Wound Healing / Q000235:genetics
D000199:Actins; D015820:Cadherins; D015815:Cell Adhesion Molecules; C102177:Evl protein, mouse; C502403:FAT1 protein, human; C502406:fat1 protein, mouse