DCC-Mediated Dab1 Phosphorylation Participates in the Multipolar-to-Bipolar Transition of Migrating Neurons

Jian Hua Zhang; Yi Fei Zhao; Xiao Xiao He; Yang Zhao; Zi Xuan He; Lei Zhang; Ying Huang; Yu Bing Wang; Ling Hu; Lin Liu; Hua Li Yu; Jia Hui Xu; Ming Ming Lai; Dong Dong Zhao; Lei Cui; Wei Xiang Guo; Wencheng Xiong; Yu Qiang Ding; Xiao Juan Zhu

doi:10.1016/j.celrep.2018.03.005

DCC-Mediated Dab1 Phosphorylation Participates in the Multipolar-to-Bipolar Transition of Migrating Neurons

Jian Hua Zhang, Yi Fei Zhao, Xiao Xiao He, Yang Zhao, Zi Xuan He, Lei Zhang, Ying Huang, Yu Bing Wang, Ling Hu, Lin Liu, Hua Li Yu, Jia Hui Xu, Ming Ming Lai, Dong Dong Zhao, Lei Cui, Wei Xiang Guo, Wencheng Xiong, Yu Qiang Ding, Xiao Juan Zhu

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19 Scopus citations

Abstract

Newborn neurons undergo inside-out migration to their final destinations during neocortical development. Reelin-induced tyrosine phosphorylation of disabled 1 (Dab1) is a critical mechanism controlling cortical neuron migration. However, the roles of Reelin-independent phosphorylation of Dab1 remain unclear. Here, we report that deleted in colorectal carcinoma (DCC) interacts with Dab1 via its P3 domain. Netrin 1, a DCC ligand, induces Dab1 phosphorylation at Y220 and Y232. Interestingly, knockdown of DCC or truncation of its P3 domain dramatically delays neuronal migration and impairs the multipolar-to-bipolar transition of migrating neurons. Notably, the migration delay and morphological transition defects are rescued by the expression of a phospho-mimetic Dab1 or a constitutively active form of Fyn proto-oncogene (Fyn), a member of the Src-family tyrosine kinases that effectively induces Dab1 phosphorylation. Collectively, these findings illustrate a DCC-Dab1 interaction that ensures proper neuronal migration during neocortical development. Non-Reelin-induced Dab1 phosphorylation was previously identified, but not characterized. Zhang et al. find that DCC interacts with Dab1, and DCC-mediated signaling effectively induces Dab1 phosphorylation. The DCC/Dab1 signaling complex is essential for neuronal migration, especially during the multipolar-to-bipolar transition.

Original language	English (US)
Pages (from-to)	3598-3611
Number of pages	14
Journal	Cell Reports
Volume	22
Issue number	13
DOIs	https://doi.org/10.1016/j.celrep.2018.03.005
State	Published - Mar 27 2018

Keywords

DCC
Dab1
Fyn
Reelin
morphological transition
neocortex development
netrin 1
neuronal migration
tyrosine phosphorylation

ASJC Scopus subject areas

Biochemistry, Genetics and Molecular Biology(all)

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10.1016/j.celrep.2018.03.005

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Zhang, J. H., Zhao, Y. F., He, X. X., Zhao, Y., He, Z. X., Zhang, L., Huang, Y., Wang, Y. B., Hu, L., Liu, L., Yu, H. L., Xu, J. H., Lai, M. M., Zhao, D. D., Cui, L., Guo, W. X., Xiong, W., Ding, Y. Q., & Zhu, X. J. (2018). DCC-Mediated Dab1 Phosphorylation Participates in the Multipolar-to-Bipolar Transition of Migrating Neurons. Cell Reports, 22(13), 3598-3611. https://doi.org/10.1016/j.celrep.2018.03.005

Zhang, JH, Zhao, YF, He, XX, Zhao, Y, He, ZX, Zhang, L, Huang, Y, Wang, YB, Hu, L, Liu, L, Yu, HL, Xu, JH, Lai, MM, Zhao, DD, Cui, L, Guo, WX, Xiong, W, Ding, YQ & Zhu, XJ 2018, 'DCC-Mediated Dab1 Phosphorylation Participates in the Multipolar-to-Bipolar Transition of Migrating Neurons', Cell Reports, vol. 22, no. 13, pp. 3598-3611. https://doi.org/10.1016/j.celrep.2018.03.005

@article{bedd2e53916d41a9b6a02fe852eec57f,

title = "DCC-Mediated Dab1 Phosphorylation Participates in the Multipolar-to-Bipolar Transition of Migrating Neurons",

abstract = "Newborn neurons undergo inside-out migration to their final destinations during neocortical development. Reelin-induced tyrosine phosphorylation of disabled 1 (Dab1) is a critical mechanism controlling cortical neuron migration. However, the roles of Reelin-independent phosphorylation of Dab1 remain unclear. Here, we report that deleted in colorectal carcinoma (DCC) interacts with Dab1 via its P3 domain. Netrin 1, a DCC ligand, induces Dab1 phosphorylation at Y220 and Y232. Interestingly, knockdown of DCC or truncation of its P3 domain dramatically delays neuronal migration and impairs the multipolar-to-bipolar transition of migrating neurons. Notably, the migration delay and morphological transition defects are rescued by the expression of a phospho-mimetic Dab1 or a constitutively active form of Fyn proto-oncogene (Fyn), a member of the Src-family tyrosine kinases that effectively induces Dab1 phosphorylation. Collectively, these findings illustrate a DCC-Dab1 interaction that ensures proper neuronal migration during neocortical development. Non-Reelin-induced Dab1 phosphorylation was previously identified, but not characterized. Zhang et al. find that DCC interacts with Dab1, and DCC-mediated signaling effectively induces Dab1 phosphorylation. The DCC/Dab1 signaling complex is essential for neuronal migration, especially during the multipolar-to-bipolar transition.",

keywords = "DCC, Dab1, Fyn, Reelin, morphological transition, neocortex development, netrin 1, neuronal migration, tyrosine phosphorylation",

author = "Zhang, {Jian Hua} and Zhao, {Yi Fei} and He, {Xiao Xiao} and Yang Zhao and He, {Zi Xuan} and Lei Zhang and Ying Huang and Wang, {Yu Bing} and Ling Hu and Lin Liu and Yu, {Hua Li} and Xu, {Jia Hui} and Lai, {Ming Ming} and Zhao, {Dong Dong} and Lei Cui and Guo, {Wei Xiang} and Wencheng Xiong and Ding, {Yu Qiang} and Zhu, {Xiao Juan}",

note = "Funding Information: This work was supported by grants from the Program of International S and T Cooperation ( 2015DFA31580 ), the National Natural Science Foundation of China ( 31271486 , 31401192 , 31671065 , 31601128 , 81571332 , and 91232724 ), the National Key R&D Program of China ( 2017YFA0104002 ), the Jilin Provincial Key Laboratory of Neural Plasticity ( 20140622001JC and 20160622020JC ), and the Fundamental Research Funds for the Central Universities of China ( 2412015KJ016 ). W.G. was funded by the Recruitment Program of the Global Youth Experts of China, 2015 . This work was also supported by the State Key Laboratory of Molecular Developmental Biology, China . We are also very grateful to Dr. Jonathan A. Cooper (Fred Hutchinson Cancer Research Center, Seattle, WA, USA) for providing the expression vectors with constitutively inactive and active Fyn mutants. Publisher Copyright: {\textcopyright} 2018 The Authors",

year = "2018",

month = mar,

day = "27",

doi = "10.1016/j.celrep.2018.03.005",

language = "English (US)",

volume = "22",

pages = "3598--3611",

journal = "Cell Reports",

issn = "2211-1247",

publisher = "Cell Press",

number = "13",

}

TY - JOUR

T1 - DCC-Mediated Dab1 Phosphorylation Participates in the Multipolar-to-Bipolar Transition of Migrating Neurons

AU - Zhang, Jian Hua

AU - Zhao, Yi Fei

AU - He, Xiao Xiao

AU - Zhao, Yang

AU - He, Zi Xuan

AU - Zhang, Lei

AU - Huang, Ying

AU - Wang, Yu Bing

AU - Hu, Ling

AU - Liu, Lin

AU - Yu, Hua Li

AU - Xu, Jia Hui

AU - Lai, Ming Ming

AU - Zhao, Dong Dong

AU - Cui, Lei

AU - Guo, Wei Xiang

AU - Xiong, Wencheng

AU - Ding, Yu Qiang

AU - Zhu, Xiao Juan

N1 - Funding Information: This work was supported by grants from the Program of International S and T Cooperation ( 2015DFA31580 ), the National Natural Science Foundation of China ( 31271486 , 31401192 , 31671065 , 31601128 , 81571332 , and 91232724 ), the National Key R&D Program of China ( 2017YFA0104002 ), the Jilin Provincial Key Laboratory of Neural Plasticity ( 20140622001JC and 20160622020JC ), and the Fundamental Research Funds for the Central Universities of China ( 2412015KJ016 ). W.G. was funded by the Recruitment Program of the Global Youth Experts of China, 2015 . This work was also supported by the State Key Laboratory of Molecular Developmental Biology, China . We are also very grateful to Dr. Jonathan A. Cooper (Fred Hutchinson Cancer Research Center, Seattle, WA, USA) for providing the expression vectors with constitutively inactive and active Fyn mutants. Publisher Copyright: © 2018 The Authors

PY - 2018/3/27

Y1 - 2018/3/27

N2 - Newborn neurons undergo inside-out migration to their final destinations during neocortical development. Reelin-induced tyrosine phosphorylation of disabled 1 (Dab1) is a critical mechanism controlling cortical neuron migration. However, the roles of Reelin-independent phosphorylation of Dab1 remain unclear. Here, we report that deleted in colorectal carcinoma (DCC) interacts with Dab1 via its P3 domain. Netrin 1, a DCC ligand, induces Dab1 phosphorylation at Y220 and Y232. Interestingly, knockdown of DCC or truncation of its P3 domain dramatically delays neuronal migration and impairs the multipolar-to-bipolar transition of migrating neurons. Notably, the migration delay and morphological transition defects are rescued by the expression of a phospho-mimetic Dab1 or a constitutively active form of Fyn proto-oncogene (Fyn), a member of the Src-family tyrosine kinases that effectively induces Dab1 phosphorylation. Collectively, these findings illustrate a DCC-Dab1 interaction that ensures proper neuronal migration during neocortical development. Non-Reelin-induced Dab1 phosphorylation was previously identified, but not characterized. Zhang et al. find that DCC interacts with Dab1, and DCC-mediated signaling effectively induces Dab1 phosphorylation. The DCC/Dab1 signaling complex is essential for neuronal migration, especially during the multipolar-to-bipolar transition.

AB - Newborn neurons undergo inside-out migration to their final destinations during neocortical development. Reelin-induced tyrosine phosphorylation of disabled 1 (Dab1) is a critical mechanism controlling cortical neuron migration. However, the roles of Reelin-independent phosphorylation of Dab1 remain unclear. Here, we report that deleted in colorectal carcinoma (DCC) interacts with Dab1 via its P3 domain. Netrin 1, a DCC ligand, induces Dab1 phosphorylation at Y220 and Y232. Interestingly, knockdown of DCC or truncation of its P3 domain dramatically delays neuronal migration and impairs the multipolar-to-bipolar transition of migrating neurons. Notably, the migration delay and morphological transition defects are rescued by the expression of a phospho-mimetic Dab1 or a constitutively active form of Fyn proto-oncogene (Fyn), a member of the Src-family tyrosine kinases that effectively induces Dab1 phosphorylation. Collectively, these findings illustrate a DCC-Dab1 interaction that ensures proper neuronal migration during neocortical development. Non-Reelin-induced Dab1 phosphorylation was previously identified, but not characterized. Zhang et al. find that DCC interacts with Dab1, and DCC-mediated signaling effectively induces Dab1 phosphorylation. The DCC/Dab1 signaling complex is essential for neuronal migration, especially during the multipolar-to-bipolar transition.

KW - DCC

KW - Dab1

KW - Fyn

KW - Reelin

KW - morphological transition

KW - neocortex development

KW - netrin 1

KW - neuronal migration

KW - tyrosine phosphorylation

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U2 - 10.1016/j.celrep.2018.03.005

DO - 10.1016/j.celrep.2018.03.005

M3 - Article

AN - SCOPUS:85043998185

SN - 2211-1247

VL - 22

SP - 3598

EP - 3611

JO - Cell Reports

JF - Cell Reports

IS - 13

ER -

DCC-Mediated Dab1 Phosphorylation Participates in the Multipolar-to-Bipolar Transition of Migrating Neurons

Abstract

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