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Publication : The WAVE regulatory complex interacts with Boc and is required for Shh-mediated axon guidance.

First Author  Balekoglu N Year  2024
Journal  iScience Volume  27
Issue  12 Pages  111333
PubMed ID  39640588 Mgi Jnum  J:359195
Mgi Id  MGI:7786222 Doi  10.1016/j.isci.2024.111333
Citation  Balekoglu N, et al. (2024) The WAVE regulatory complex interacts with Boc and is required for Shh-mediated axon guidance. iScience 27(12):111333
abstractText  During development, Shh attracts axons of spinal cord commissural neurons to the floor plate. Shh-mediated attraction of commissural axons requires the receptor Boc. How Boc regulates cytoskeletal changes in growth cones in response to Shh is not fully understood. To identify effectors of Boc in Shh-mediated axon guidance, we used BioID to screen for proteins in proximity to Boc. Top hits included members of the WAVE regulatory complex (WRC), which acts downstream of Rac1 to promote actin cytoskeleton assembly. Therefore, we hypothesized that the WRC is important for Shh-mediated growth cone turning. Using biochemical and cellular assays, we found that Boc directly interacts with the WRC and that this interaction can occur in live cells. Moreover, we found that knockdown of Nckap1 and Cyfip1/2, two subunits of the WRC, in commissural neurons, impairs axon attraction toward a Shh gradient. Our results demonstrate that the WRC is required for Shh-mediated axon attraction.
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