Trio Is a Key Guanine Nucleotide Exchange Factor Coordinating Regulation of the Migration and Morphogenesis of Granule Cells in the Developing Cerebellum

Orchestrated regulation of neuronal migration and morphogenesis is critical for neuronal development and establishment of functional circuits, but its regulatory mechanism is incompletely defined. We established and analyzed mice with neural-specific knock-out of Trio, a guanine nucleotide exchange...

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Bibliographic Details
Published in:The Journal of biological chemistry 2010-08, Vol.285 (32), p.24834-24844
Main Authors: Peng, Ya-Jing, He, Wei-Qi, Tang, Jing, Tao, Tao, Chen, Chen, Gao, Yun-Qian, Zhang, Wen-Cheng, He, Xue-Yan, Dai, Yu-Yuan, Zhu, Nian-Chun, Lv, Ning, Zhang, Cheng-Hai, Qiao, Yan-Ning, Zhao, Li-Ping, Gao, Xiang, Zhu, Min-Sheng
Format: Article
Language:English
Subjects:
Animals
Cell Migration
Cell Movement
Cerebellum - embryology
Chromosomes, Artificial, Bacterial - metabolism
Cytoskeleton
Cytoskeleton - metabolism
Developmental Biology
Gene Expression Regulation, Developmental
Gene Knockout
Glial Fibrillary Acidic Protein - metabolism
Guanine Nucleotide Exchange Factor
Guanine Nucleotide Exchange Factors - chemistry
Guanine Nucleotide Exchange Factors - genetics
Guanine Nucleotide Exchange Factors - physiology
Intermediate Filament Proteins - metabolism
Mice
Mice, Knockout
Morphogenesis
Nerve Tissue Proteins - metabolism
Nestin
Neurodevelopment
Neurons - metabolism
Parallel Fiber
Phosphoproteins - genetics
Phosphoproteins - physiology
Protein-Serine-Threonine Kinases - genetics
Protein-Serine-Threonine Kinases - physiology
rho GTP-Binding Proteins - metabolism
Signal Transduction
Small GTPase
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Summary:Orchestrated regulation of neuronal migration and morphogenesis is critical for neuronal development and establishment of functional circuits, but its regulatory mechanism is incompletely defined. We established and analyzed mice with neural-specific knock-out of Trio, a guanine nucleotide exchange factor with multiple guanine nucleotide exchange factor domains. Knock-out mice showed defective cerebella and severe signs of ataxia. Mutant cerebella had no granule cells in the internal granule cell layer due to aberrant granule cell migration as well as abnormal neurite growth. Trio-deficient granule cells showed reduced extension of neurites and highly branched and misguided processes with perturbed stabilization of actin and microtubules. Trio deletion caused down-regulation of the activation of Rac1, RhoA, and Cdc42, and mutant granule cells appeared to be unresponsive to neurite growth-promoting molecules such as Netrin-1 and Semaphorin 6A. These results suggest that Trio may be a key signal module for the orchestrated regulation of neuronal migration and morphogenesis during cerebellar development. Trio may serve as a signal integrator decoding extrinsic signals to Rho GTPases for cytoskeleton organization.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M109.096537