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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.

SUBMITTER: Huang PT

PROVIDER: S-EPMC4324908 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Huntingtin-associated protein 1 interacts with breakpoint cluster region protein to regulate neuronal differentiation.

Huang Pai-Tsang PT Chen Chien-Ho CH Hsu I-Uen IU Salim Shaima'a Ahmad SA Kao Shu-Huei SH Cheng Chao-Wen CW Lai Chang-Hao CH Lee Cheng-Fan CF Lin Yung-Feng YF

PloS one 20150211 2

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, hypothal ...[more]

PMID: 25671650

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Huntingtin-associated protein 1 interacts with breakpoint cluster region protein to regulate neuronal differentiation.

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Huntingtin-associated protein 1 interacts with breakpoint cluster region protein to regulate neuronal differentiation.

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