Contact-dependent promotion of cell migration by the OL-protocadherin-Nap1 interaction.
OL-protocadherin (OL-pc) is a transmembrane protein belonging to the cadherin superfamily, which has been shown to accumulate at cell-cell contacts via its homophilic interaction, but its molecular roles remain elusive. In this study, we show that OL-pc bound Nck-associated protein 1 (Nap1), a protein that regulates WAVE-mediated actin assembly. In astrocytoma U251 cells not expressing OL-pc, Nap1 was localized only along the lamellipodia. However, exogenous expression of OL-pc in these cells recruited Nap1 as well as WAVE1 to cell-cell contact sites. Although OL-pc expression had no effect on the motility of solitary U251 cells, it accelerated their movement when they were in contact with one another, causing concomitant reorganization of F-actin and N-cadherin at cell junctions. OL-pc mutants lacking the Nap1-binding site exhibited no such effect. N-cadherin knockdown mimicked OL-pc expression in enhancing cell movement. These results suggest that OL-pc remodels the motility and adhesion machinery at cell junctions by recruiting the Nap1-WAVE1 complex to these sites and, in turn, promotes the migration of cells.
Nakao
Shinsuke
S
Graduate School of Biostudies, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan.
Platek
Anna
A
Hirano
Shinji
S
Takeichi
Masatoshi
M
D000199:Actins / Q000378:metabolism; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D019556:COS Cells; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D002448:Cell Adhesion / Q000502:physiology; D002450:Cell Communication / Q000502:physiology*; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism*; D002465:Cell Movement / Q000502:physiology*; D002522:Chlorocebus aethiops; D006801:Humans; D007365:Intercellular Junctions / Q000378:metabolism; D011506:Proteins / Q000378:metabolism*; D000091363:Protocadherins; D011554:Pseudopodia / Q000378:metabolism; D051381:Rats; D051300:Wiskott-Aldrich Syndrome Protein Family / Q000378:metabolism; D012359:tRNA Methyltransferases
D000199:Actins; D015703:Antigens, CD; C050361:CDH2 protein, human; D015820:Cadherins; C438603:PCDH10 protein, human; D011506:Proteins; D000091363:Protocadherins; C114864:WASF1 protein, human; D051300:Wiskott-Aldrich Syndrome Protein Family; C498548:TRMO protein, human; D012359:tRNA Methyltransferases