Capzb2 interacts with beta-tubulin to regulate growth cone morphology and neurite outgrowth.
Capping protein (CP) is a heterodimer that regulates actin assembly by binding to the barbed end of F-actin. In cultured nonneuronal cells, each CP subunit plays a critical role in the organization and dynamics of lamellipodia and filopodia. Mutations in either alpha or beta CP subunit result in retinal degeneration in Drosophila. However, the function of CP subunits in mammalian neurons remains unclear. Here, we investigate the role of the beta CP subunit expressed in the brain, Capzb2, in growth cone morphology and neurite outgrowth. We found that silencing Capzb2 in hippocampal neurons resulted in short neurites and misshapen growth cones in which microtubules overgrew into the periphery and completely overlapped with F-actin. In searching for the mechanisms underlying these cytoskeletal abnormalities, we identified beta-tubulin as a novel binding partner of Capzb2 and demonstrated that Capzb2 decreases the rate and the extent of tubulin polymerization in vitro. We mapped the region of Capzb2 that was required for the subunit to interact with beta-tubulin and inhibit microtubule polymerization. A mutant Capzb2 lacking this region was able to bind F-actin and form a CP heterodimer with alpha2-subunit. However, this mutant was unable to rescue the growth cone and neurite outgrowth phenotypes caused by Capzb2 knockdown. Together, these data suggest that Capzb2 plays an important role in growth cone formation and neurite outgrowth and that the underlying mechanism may involve direct interaction between Capzb2 and microtubules.
Davis
David A
DA
Department of Pathology and Laboratory Medicine, Boston University School of Medicine, Boston, Massachusetts, USA.
Wilson
Meredith H
MH
Giraud
Jodel
J
Xie
Zhigang
Z
Tseng
Huang-Chun
HC
England
Cheryl
C
Herscovitz
Haya
H
Tsai
Li-Huei
LH
Delalle
Ivana
I
D000199:Actins / Q000378:metabolism; D000818:Animals; D001665:Binding Sites; D051347:CapZ Actin Capping Protein / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D019281:Dimerization; D020439:Growth Cones / Q000502:physiology / Q000648:ultrastructure*; D006624:Hippocampus / Q000378:metabolism / Q000648:ultrastructure; D051379:Mice; D008870:Microtubules / Q000378:metabolism; D009154:Mutation; D009416:Nerve Regeneration; D016501:Neurites / Q000648:ultrastructure; D034622:RNA Interference; D014404:Tubulin / Q000378:metabolism / Q000502:physiology*
D000199:Actins; D051347:CapZ Actin Capping Protein; D014404:Tubulin