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

Pai Tsang Huang, Chien Ho Chen, I. Uen Hsu, Shaima'a Ahmad Salim, Shu Huei Kao, Chao Wen Cheng, Chang Hao Lai, Cheng Fan Lee, Yung Feng Lin

Research output: Contribution to journalArticle

9 Citations (Scopus)

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 languageEnglish
Article numbere0116372
JournalPLoS One
Volume10
Issue number2
DOIs
Publication statusPublished - Feb 11 2015

Fingerprint

Proto-Oncogene Proteins c-bcr
Microtubules
Proteins
proteins
Extracellular Signal-Regulated MAP Kinases
microtubules
Brain
rho GTP-Binding Proteins
Microtubule-Associated Proteins
Neurodegenerative diseases
mitogen-activated protein kinase
Paclitaxel
Huntingtin Protein
Tropomyosin
Neurodegenerative Diseases
Proteomics
Hypothalamus
mice
Protein Isoforms
brain

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 journalArticle

@article{8f6104d86ebd44e9b6481491177c1c8c,
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 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.",
author = "Huang, {Pai Tsang} and Chen, {Chien Ho} and Hsu, {I. Uen} and Salim, {Shaima'a Ahmad} and Kao, {Shu Huei} and Cheng, {Chao Wen} and Lai, {Chang Hao} and Lee, {Cheng Fan} and Lin, {Yung Feng}",
year = "2015",
month = "2",
day = "11",
doi = "10.1371/journal.pone.0116372",
language = "English",
volume = "10",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "2",

}

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.

UR - http://www.scopus.com/inward/record.url?scp=84923013459&partnerID=8YFLogxK

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 -