| First Author | Huang PT | Year | 2015 |
| Journal | PLoS One | Volume | 10 |
| Issue | 2 | Pages | e0116372 |
| PubMed ID | 25671650 | Mgi Jnum | J:229041 |
| Mgi Id | MGI:5750265 | Doi | 10.1371/journal.pone.0116372 |
| Citation | Huang PT, et al. (2015) Huntingtin-associated protein 1 interacts with breakpoint cluster region protein to regulate neuronal differentiation. PLoS One 10(2):e0116372 |
| abstractText | Alterations in microtubule-dependent trafficking and certain signaling pathways in neuronal cells represent critical pathogenesis in neurodegenerative diseases. Huntingtin (Htt)-associated protein-1 (Hap1) is a brain-enriched protein and plays a key role in the trafficking of neuronal surviving and differentiating cargos. Lack of Hap1 reduces signaling through tropomyosin-related kinases including extracellular signal regulated kinase (ERK), resulting in inhibition of neurite outgrowth, hypothalamic dysfunction and postnatal lethality in mice. To examine how Hap1 is involved in microtubule-dependent trafficking and neuronal differentiation, we performed a proteomic analysis using taxol-precipitated microtubules from Hap1-null and wild-type mouse brains. Breakpoint cluster region protein (Bcr), a Rho GTPase regulator, was identified as a Hap1-interacting partner. Bcr was co-immunoprecipitated with Hap1 from transfected neuro-2a cells and co-localized with Hap1A isoform more in the differentiated than in the nondifferentiated cells. The Bcr downstream effectors, namely ERK and p38, were significantly less activated in Hap1-null than in wild-type mouse hypothalamus. In conclusion, Hap1 interacts with Bcr on microtubules to regulate neuronal differentiation. |
