Roles of Collagen XXV and Its Putative Receptors PTPσ/δ in Intramuscular Motor Innervation and Congenital Cranial Dysinnervation Disorder
Summary: Intramuscular motor innervation is an essential process in neuromuscular development. Recently, mutations in COL25A1, encoding CLAC-P/collagen XXV, have been linked to the development of a congenital cranial dysinnervation disorder (CCDD). Yet the molecular mechanisms of intramuscular inner...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2019-12-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124719316353 |
| _version_ | 1818321669586944000 |
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| author | Haruka Munezane Hiroaki Oizumi Tomoko Wakabayashi Shu Nishio Tomoko Hirasawa Takashi Sato Akihiro Harada Tomoyuki Yoshida Takahiro Eguchi Yuji Yamanashi Tadafumi Hashimoto Takeshi Iwatsubo |
| author_facet | Haruka Munezane Hiroaki Oizumi Tomoko Wakabayashi Shu Nishio Tomoko Hirasawa Takashi Sato Akihiro Harada Tomoyuki Yoshida Takahiro Eguchi Yuji Yamanashi Tadafumi Hashimoto Takeshi Iwatsubo |
| author_sort | Haruka Munezane |
| collection | DOAJ |
| description | Summary: Intramuscular motor innervation is an essential process in neuromuscular development. Recently, mutations in COL25A1, encoding CLAC-P/collagen XXV, have been linked to the development of a congenital cranial dysinnervation disorder (CCDD). Yet the molecular mechanisms of intramuscular innervation and the etiology of CCDD related to COL25A1 have remained elusive. Here, we report that muscle-derived collagen XXV is indispensable for intramuscular innervation. In developing skeletal muscles, Col25a1 expression is tightly regulated by muscle excitation. In vitro and cell-based assays reveal a direct interaction between collagen XXV and receptor protein tyrosine phosphatases (PTPs) σ and δ. Motor explant assays show that expression of collagen XXV in target cells attracts motor axons, but this is inhibited by exogenous PTPσ/δ. CCDD mutations attenuate motor axon attraction by reducing collagen XXV-PTPσ/δ interaction. Overall, our study identifies PTPσ/δ as putative receptors for collagen XXV, implicating collagen XXV and PTPσ/δ in intramuscular innervation and a developmental ocular motor disorder. : Munezane et al. demonstrate essential roles of muscle-derived collagen XXV in motor axon attraction and intramuscular innervation during development. Collagen XXV interacts with motor axons through its putative receptors PTPσ/δ. Congenital cranial dysinnervation disorder-causing mutations in collagen XXV attenuate the interaction with PTPσ/δ and disrupt innervation by motor axons. Keywords: motor neuron, neuromuscular development, collagen, receptor protein tyrosine phosphatase |
| first_indexed | 2024-12-13T10:44:35Z |
| format | Article |
| id | doaj.art-9f7b9257524b4cf0896c2cc86be8f09d |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-13T10:44:35Z |
| publishDate | 2019-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-9f7b9257524b4cf0896c2cc86be8f09d2022-12-21T23:50:17ZengElsevierCell Reports2211-12472019-12-01291343624376.e6Roles of Collagen XXV and Its Putative Receptors PTPσ/δ in Intramuscular Motor Innervation and Congenital Cranial Dysinnervation DisorderHaruka Munezane0Hiroaki Oizumi1Tomoko Wakabayashi2Shu Nishio3Tomoko Hirasawa4Takashi Sato5Akihiro Harada6Tomoyuki Yoshida7Takahiro Eguchi8Yuji Yamanashi9Tadafumi Hashimoto10Takeshi Iwatsubo11Department of Neuropathology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, JapanDepartment of Neuropathology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, JapanDepartment of Neuropathology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan; Department of Innovative Dementia Prevention, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan; Corresponding authorDepartment of Neuropathology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, JapanDepartment of Neuropathology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, JapanLaboratory of Developmental Biology and Metabolism, Institute for Molecular and Cellular Regulation, Gunma University, Gunma 371-8512, JapanDepartment of Cell Biology, Graduate School of Medicine, Osaka University, Osaka 565-0871, JapanDepartment of Molecular Neuroscience, University of Toyama, Toyama 930-0194, JapanDivision of Genetics, Department of Cancer Biology, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, JapanDivision of Genetics, Department of Cancer Biology, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, JapanDepartment of Neuropathology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan; Department of Innovative Dementia Prevention, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, JapanDepartment of Neuropathology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan; Corresponding authorSummary: Intramuscular motor innervation is an essential process in neuromuscular development. Recently, mutations in COL25A1, encoding CLAC-P/collagen XXV, have been linked to the development of a congenital cranial dysinnervation disorder (CCDD). Yet the molecular mechanisms of intramuscular innervation and the etiology of CCDD related to COL25A1 have remained elusive. Here, we report that muscle-derived collagen XXV is indispensable for intramuscular innervation. In developing skeletal muscles, Col25a1 expression is tightly regulated by muscle excitation. In vitro and cell-based assays reveal a direct interaction between collagen XXV and receptor protein tyrosine phosphatases (PTPs) σ and δ. Motor explant assays show that expression of collagen XXV in target cells attracts motor axons, but this is inhibited by exogenous PTPσ/δ. CCDD mutations attenuate motor axon attraction by reducing collagen XXV-PTPσ/δ interaction. Overall, our study identifies PTPσ/δ as putative receptors for collagen XXV, implicating collagen XXV and PTPσ/δ in intramuscular innervation and a developmental ocular motor disorder. : Munezane et al. demonstrate essential roles of muscle-derived collagen XXV in motor axon attraction and intramuscular innervation during development. Collagen XXV interacts with motor axons through its putative receptors PTPσ/δ. Congenital cranial dysinnervation disorder-causing mutations in collagen XXV attenuate the interaction with PTPσ/δ and disrupt innervation by motor axons. Keywords: motor neuron, neuromuscular development, collagen, receptor protein tyrosine phosphatasehttp://www.sciencedirect.com/science/article/pii/S2211124719316353 |
| spellingShingle | Haruka Munezane Hiroaki Oizumi Tomoko Wakabayashi Shu Nishio Tomoko Hirasawa Takashi Sato Akihiro Harada Tomoyuki Yoshida Takahiro Eguchi Yuji Yamanashi Tadafumi Hashimoto Takeshi Iwatsubo Roles of Collagen XXV and Its Putative Receptors PTPσ/δ in Intramuscular Motor Innervation and Congenital Cranial Dysinnervation Disorder Cell Reports |
| title | Roles of Collagen XXV and Its Putative Receptors PTPσ/δ in Intramuscular Motor Innervation and Congenital Cranial Dysinnervation Disorder |
| title_full | Roles of Collagen XXV and Its Putative Receptors PTPσ/δ in Intramuscular Motor Innervation and Congenital Cranial Dysinnervation Disorder |
| title_fullStr | Roles of Collagen XXV and Its Putative Receptors PTPσ/δ in Intramuscular Motor Innervation and Congenital Cranial Dysinnervation Disorder |
| title_full_unstemmed | Roles of Collagen XXV and Its Putative Receptors PTPσ/δ in Intramuscular Motor Innervation and Congenital Cranial Dysinnervation Disorder |
| title_short | Roles of Collagen XXV and Its Putative Receptors PTPσ/δ in Intramuscular Motor Innervation and Congenital Cranial Dysinnervation Disorder |
| title_sort | roles of collagen xxv and its putative receptors ptpσ δ in intramuscular motor innervation and congenital cranial dysinnervation disorder |
| url | http://www.sciencedirect.com/science/article/pii/S2211124719316353 |
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