title: Huntingtin-associated protein 1 interacts with breakpoint cluster region protein to regulate neuronal differentiation.
abstract: 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.
authors: Department of Occupational Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.
authors: Pai-Tsang
authors: PT
authors: Huang
authors: School of Medical Laboratory Science and Biotechnology, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.
authors: Chien-Ho
authors: CH
authors: Chen
authors: School of Medical Laboratory Science and Biotechnology, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.
authors: I-Uen
authors: IU
authors: Hsu
authors: School of Medical Laboratory Science and Biotechnology, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.
authors: Shaima'a Ahmad
authors: SA
authors: Salim
authors: School of Medical Laboratory Science and Biotechnology, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.
authors: Shu-Huei
authors: SH
authors: Kao
authors: Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
authors: Chao-Wen
authors: CW
authors: Cheng
authors: Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan.
authors: Chang-Hao
authors: CH
authors: Lai
authors: School of Medical Laboratory Science and Biotechnology, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.
authors: Cheng-Fan
authors: CF
authors: Lee
authors: School of Medical Laboratory Science and Biotechnology, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.
authors: Yung-Feng
authors: YF
authors: Lin
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D002460:Cell Line; D005260:Female; D007031:Hypothalamus / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008870:Microtubules / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000166:cytology* / Q000378:metabolism*; D011485:Protein Binding; D021381:Protein Transport; D051562:Proto-Oncogene Proteins c-bcr / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: C490758:Hap1 protein, mouse; D009419:Nerve Tissue Proteins; D051562:Proto-Oncogene Proteins c-bcr