Capping protein is essential for cell migration in vivo and for filopodial morphology and dynamics.
Capping protein (CP) binds to barbed ends of growing actin filaments and inhibits elongation. CP is essential for actin-based motility in cell-free systems and in Dictyostelium. Even though CP is believed to be critical for creating the lamellipodial actin structure necessary for protrusion and migration, CP's role in mammalian cell migration has not been directly tested. Moreover, recent studies have suggested that structures besides lamellipodia, including lamella and filopodia, may have unappreciated roles in cell migration. CP has been postulated to be absent from filopodia, and thus its role in filopodial activity has remained unexplored. We report that silencing CP in both cultured mammalian B16F10 cells and in neurons of developing neocortex impaired cell migration. Moreover, we unexpectedly observed that low levels of CP were detectable in the majority of filopodia. CP depletion decreased filopodial length, altered filopodial shape, and reduced filopodial dynamics. Our results support an expansion of the potential roles that CP plays in cell motility by implicating CP in filopodia as well as in lamellipodia, both of which are important for locomotion in many types of migrating cells.
Division of Biological Sciences, University of California, San Diego, and Sanford Consortium for Regenerative Medicine, La Jolla, CA 92037.
Shamim A
SA
Sinnar
Fred Hutchinson Cancer Research Center, Seattle, WA 98109.
Susumu
S
Antoku
Division of Biological Sciences, University of California, San Diego, and Sanford Consortium for Regenerative Medicine, La Jolla, CA 92037.
Jean-Michel
JM
Saffin
Fred Hutchinson Cancer Research Center, Seattle, WA 98109.
Jon A
JA
Cooper
Division of Biological Sciences, University of California, San Diego, and Sanford Consortium for Regenerative Medicine, La Jolla, CA 92037 shalpain@ucsd.edu.
Shelley
S
Halpain
D000199:Actins / Q000378:metabolism; D000818:Animals; D051347:CapZ Actin Capping Protein / Q000502:physiology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D048430:Cell Shape; D055785:Gene Knockdown Techniques; D051379:Mice; D011554:Pseudopodia / Q000378:metabolism / Q000648:ultrastructure*
D000199:Actins; D051347:CapZ Actin Capping Protein