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 coimmunoprecipitated 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.
| Original language | English |
|---|---|
| Article number | e0116372 |
| Journal | PLoS One |
| Volume | 10 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - Feb 11 2015 |
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ASJC Scopus subject areas
- Agricultural and Biological Sciences(all)
- Biochemistry, Genetics and Molecular Biology(all)
- Medicine(all)
Cite this
Huntingtin-associated protein 1 interacts with breakpoint cluster region protein to regulate neuronal differentiation. / Huang, Pai Tsang; Chen, Chien Ho; Hsu, I. Uen; Salim, Shaima'a Ahmad; Kao, Shu Huei; Cheng, Chao Wen; Lai, Chang Hao; Lee, Cheng Fan; Lin, Yung Feng.
In: PLoS One, Vol. 10, No. 2, e0116372, 11.02.2015.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Huntingtin-associated protein 1 interacts with breakpoint cluster region protein to regulate neuronal differentiation
AU - Huang, Pai Tsang
AU - Chen, Chien Ho
AU - Hsu, I. Uen
AU - Salim, Shaima'a Ahmad
AU - Kao, Shu Huei
AU - Cheng, Chao Wen
AU - Lai, Chang Hao
AU - Lee, Cheng Fan
AU - Lin, Yung Feng
PY - 2015/2/11
Y1 - 2015/2/11
N2 - 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 coimmunoprecipitated 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.
AB - 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 coimmunoprecipitated 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=84923013459&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0116372
DO - 10.1371/journal.pone.0116372
M3 - Article
C2 - 25671650
AN - SCOPUS:84923013459
VL - 10
JO - PLoS One
JF - PLoS One
SN - 1932-6203
IS - 2
M1 - e0116372
ER -