α2-chimaerin is required for Eph receptor-class-specific spinal motor axon guidance and coordinate activation of antagonistic muscles

Tzu Jen Kao, Georgina C B Nicholl, Jamie A. Johansen, Artur Kania, Asim A. Beg

研究成果: 雜誌貢獻文章

13 引文 (Scopus)

摘要

Axonal guidance involves extrinsic molecular cues that bind growth cone receptors and signal to the cytoskeleton through divergent pathways. Some signaling intermediates are deployed downstream of molecularly distinct axon guidance receptor families, but the scope of this overlap is unclear, as is the impact of embryonic axon guidance fidelity on adult nervous system function. Here, we demonstrate that the Rho-GTPase-activating protein α2-chimaerin is specifically required for EphA and not EphB receptor signaling in mouse and chick spinal motor axons. Reflecting this specificity, the loss of α2-chimaerin function disrupts the limb trajectory of extensor-muscle-innervating motor axons the guidance of which depends on EphA signaling. These embryonic defects affect coordinated contraction of antagonistic flexor-extensor muscles in the adult, indicating that accurate embryonic motor axon guidance is critical for optimal neuromuscular function. Together, our observations provide the first functional evidence of an Eph receptor-class-specific intracellular signaling protein that is required for appropriate neuromuscular connectivity.
原文英語
頁(從 - 到)2344-2357
頁數14
期刊Journal of Neuroscience
35
發行號6
DOIs
出版狀態已發佈 - 2015

指紋

EphA1 Receptor
Muscles
Intracellular Signaling Peptides and Proteins
Eph Family Receptors
Growth Cones
Cytoskeleton
Nervous System
Cues
Axons
Extremities
Axon Guidance

ASJC Scopus subject areas

  • Neuroscience(all)

引用此文

α2-chimaerin is required for Eph receptor-class-specific spinal motor axon guidance and coordinate activation of antagonistic muscles. / Kao, Tzu Jen; Nicholl, Georgina C B; Johansen, Jamie A.; Kania, Artur; Beg, Asim A.

於: Journal of Neuroscience, 卷 35, 編號 6, 2015, p. 2344-2357.

研究成果: 雜誌貢獻文章

Kao, Tzu Jen ; Nicholl, Georgina C B ; Johansen, Jamie A. ; Kania, Artur ; Beg, Asim A. / α2-chimaerin is required for Eph receptor-class-specific spinal motor axon guidance and coordinate activation of antagonistic muscles. 於: Journal of Neuroscience. 2015 ; 卷 35, 編號 6. 頁 2344-2357.
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AU - Nicholl, Georgina C B

AU - Johansen, Jamie A.

AU - Kania, Artur

AU - Beg, Asim A.

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N2 - Axonal guidance involves extrinsic molecular cues that bind growth cone receptors and signal to the cytoskeleton through divergent pathways. Some signaling intermediates are deployed downstream of molecularly distinct axon guidance receptor families, but the scope of this overlap is unclear, as is the impact of embryonic axon guidance fidelity on adult nervous system function. Here, we demonstrate that the Rho-GTPase-activating protein α2-chimaerin is specifically required for EphA and not EphB receptor signaling in mouse and chick spinal motor axons. Reflecting this specificity, the loss of α2-chimaerin function disrupts the limb trajectory of extensor-muscle-innervating motor axons the guidance of which depends on EphA signaling. These embryonic defects affect coordinated contraction of antagonistic flexor-extensor muscles in the adult, indicating that accurate embryonic motor axon guidance is critical for optimal neuromuscular function. Together, our observations provide the first functional evidence of an Eph receptor-class-specific intracellular signaling protein that is required for appropriate neuromuscular connectivity.

AB - Axonal guidance involves extrinsic molecular cues that bind growth cone receptors and signal to the cytoskeleton through divergent pathways. Some signaling intermediates are deployed downstream of molecularly distinct axon guidance receptor families, but the scope of this overlap is unclear, as is the impact of embryonic axon guidance fidelity on adult nervous system function. Here, we demonstrate that the Rho-GTPase-activating protein α2-chimaerin is specifically required for EphA and not EphB receptor signaling in mouse and chick spinal motor axons. Reflecting this specificity, the loss of α2-chimaerin function disrupts the limb trajectory of extensor-muscle-innervating motor axons the guidance of which depends on EphA signaling. These embryonic defects affect coordinated contraction of antagonistic flexor-extensor muscles in the adult, indicating that accurate embryonic motor axon guidance is critical for optimal neuromuscular function. Together, our observations provide the first functional evidence of an Eph receptor-class-specific intracellular signaling protein that is required for appropriate neuromuscular connectivity.

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KW - Chimaerin

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KW - Muscle contraction

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