| First Author | Kwon Y | Year | 2020 |
| Journal | PLoS One | Volume | 15 |
| Issue | 4 | Pages | e0230814 |
| PubMed ID | 32251425 | Mgi Jnum | J:286654 |
| Mgi Id | MGI:6403798 | Doi | 10.1371/journal.pone.0230814 |
| Citation | Kwon Y, et al. (2020) betaPix-d promotes tubulin acetylation and neurite outgrowth through a PAK/Stathmin1 signaling pathway. PLoS One 15(4):e0230814 |
| abstractText | Microtubules are a major cytoskeletal component of neurites, and the regulation of microtubule stability is essential for neurite morphogenesis. betaPix (ARHGEF7) is a guanine nucleotide exchange factor for the small GTPases Rac1 and Cdc42, which modulate the organization of actin filaments and microtubules. betaPix is expressed as alternatively spliced variants, including the ubiquitous isoform betaPix-a and the neuronal isoforms betaPix-b and betaPix-d, but the function of the neuronal isoforms remains unclear. Here, we reveal the novel role of betaPix neuronal isoforms in regulating tubulin acetylation and neurite outgrowth. At DIV4, hippocampal neurons cultured from betaPix neuronal isoform knockout (betaPix-NIKO) mice exhibit defects in neurite morphology and tubulin acetylation, a type of tubulin modification which often labels stable microtubules. Treating betaPix-NIKO neurons with paclitaxel, which stabilizes the microtubules, or reintroducing either neuronal betaPix isoform to the KO neurons overcomes the impairment in neurite morphology and tubulin acetylation, suggesting that neuronal betaPix isoforms may promote microtubule stabilization during neurite development. betaPix-NIKO neurons also exhibit lower phosphorylation levels for Stathmin1, a microtubule-destabilizing protein, at Ser16. Expressing either betaPix neuronal isoform in the betaPix-NIKO neurons restores Stathmin1 phosphorylation levels, with betaPix-d having a greater effect than betaPix-b. Furthermore, we find that the recovery of neurite length and Stathmin1 phosphorylation via betaPix-d expression requires PAK kinase activity. Taken together, our study demonstrates that betaPix-d regulates the phosphorylation of Stathmin1 in a PAK-dependent manner and that neuronal betaPix isoforms promote tubulin acetylation and neurite morphogenesis during neuronal development. |
