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Title: Src-mediated phosphorylation of βpix-b regulates dendritic spine morphogenesis
Authors: Shin, Mi-seon
Song, Sang-ho
Shin, Jung Eun
Lee, Seung-Hye
Huh, Sung-Oh
Park, Dongeun
Keywords: DRNTU::Science::Medicine
Issue Date: 2019
Source: Shin, M.-s., Song, S.-h., Shin, J. E., Lee, S.-H., Huh, S.-O., & Park, D. (2019). Src-mediated phosphorylation of βPix-b regulates dendritic spine morphogenesis. Journal of Cell Science, 132(5), jcs224980-. doi:10.1242/jcs.224980
Series/Report no.: Journal of Cell Science
Abstract: PAK-interacting guanine nucleotide exchange factor (βPix; also known as Arhgef7) has been implicated in many actin-based cellular processes, including spine morphogenesis in neurons. However, the molecular mechanisms by which βPix controls spine morphology remain elusive. Previously, we have reported the expression of several alternative spliced βPix isoforms in the brain. Here, we report a novel finding that the b isoform of βPix (βPix-b) mediates the regulation of spine and synapse formation. We found that βPix-b, which is mainly expressed in neurons, enhances spine and synapse formation through preferential localization at spines. In neurons, glutamate treatment efficiently stimulates Rac1 GEF activity of βPix-b. The glutamate stimulation also promotes Src-mediated phosphorylation of βPix-b in both an AMPA receptor- and NMDA receptor-dependent manner. Tyrosine 598 (Y598) of βPix-b is identified as the major Src-mediated phosphorylation site. Finally, Y598 phosphorylation of βPix-b enhances its Rac1 GEF activity that is critical for spine and synapse formation. In conclusion, we provide a novel mechanism by which βPix-b regulates activity-dependent spinogenesis and synaptogenesis via Src-mediated phosphorylation.
ISSN: 0021-9533
DOI: 10.1242/jcs.224980
Rights: © 2019 The Author(s). Published by The Company of Biologists Ltd.
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:LKCMedicine Journal Articles

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