{"title":"CRMP2及其磷酸化可防止皮质脊髓束轴突错路","authors":"Satohiro Takizawa , Yurika Nakanishi , Yumeno Koga , Yuki Yamazaki , Papachan Kolattukudy , Yoshio Goshima , Toshio Ohshima","doi":"10.1016/j.neulet.2025.138231","DOIUrl":null,"url":null,"abstract":"<div><div>During the development of the central nervous system (CNS), the formation of neural circuits such as the corticospinal tract (CST) is crucial to control voluntary movement and is regulated by axonal guidance mechanisms.</div><div>In this study, we examined the role of CRMP2 (Collapsin response mediator protein 2) in the formation of CST. CRMP2, which binds to actin and microtubules to control the cytoskeleton, is a phosphoprotein whose activity depends on its phosphorylated state. To inhibit Cyclin-dependent kinase 5 (Cdk5) phosphorylation, CRMP2 knock-in (<em>crmp2<sup>ki/ki</sup></em>) mice were generated in which the serine residue at position 522 was replaced with alanine. Our results showed that both CRMP2 knock-out (<em>crmp2<sup>-/-</sup></em>) and <em>crmp2<sup>ki/ki</sup></em> mice exhibited higher percentages of CST axons that crossed the midline erroneously than wild-type (WT) mice. However, in mice lacking CRMP1, which is highly homologous to CRMP2, few axons crossed the midline, similar to WT mice. Additionally, <em>crmp2<sup>-/-</sup></em> and <em>crmp2<sup>ki/ki</sup></em> mice showed decreased proportions of independent forelimb movements. These findings emphasize that CRMP2 and its phosphorylation are necessary for proper CST formation in the mouse CNS.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"855 ","pages":"Article 138231"},"PeriodicalIF":2.5000,"publicationDate":"2025-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"CRMP2 and its phosphorylation prevent axonal misrouting of the corticospinal tract\",\"authors\":\"Satohiro Takizawa , Yurika Nakanishi , Yumeno Koga , Yuki Yamazaki , Papachan Kolattukudy , Yoshio Goshima , Toshio Ohshima\",\"doi\":\"10.1016/j.neulet.2025.138231\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div>During the development of the central nervous system (CNS), the formation of neural circuits such as the corticospinal tract (CST) is crucial to control voluntary movement and is regulated by axonal guidance mechanisms.</div><div>In this study, we examined the role of CRMP2 (Collapsin response mediator protein 2) in the formation of CST. CRMP2, which binds to actin and microtubules to control the cytoskeleton, is a phosphoprotein whose activity depends on its phosphorylated state. To inhibit Cyclin-dependent kinase 5 (Cdk5) phosphorylation, CRMP2 knock-in (<em>crmp2<sup>ki/ki</sup></em>) mice were generated in which the serine residue at position 522 was replaced with alanine. Our results showed that both CRMP2 knock-out (<em>crmp2<sup>-/-</sup></em>) and <em>crmp2<sup>ki/ki</sup></em> mice exhibited higher percentages of CST axons that crossed the midline erroneously than wild-type (WT) mice. However, in mice lacking CRMP1, which is highly homologous to CRMP2, few axons crossed the midline, similar to WT mice. Additionally, <em>crmp2<sup>-/-</sup></em> and <em>crmp2<sup>ki/ki</sup></em> mice showed decreased proportions of independent forelimb movements. These findings emphasize that CRMP2 and its phosphorylation are necessary for proper CST formation in the mouse CNS.</div></div>\",\"PeriodicalId\":19290,\"journal\":{\"name\":\"Neuroscience Letters\",\"volume\":\"855 \",\"pages\":\"Article 138231\"},\"PeriodicalIF\":2.5000,\"publicationDate\":\"2025-04-06\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Neuroscience Letters\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0304394025001193\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"NEUROSCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Neuroscience Letters","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0304394025001193","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"NEUROSCIENCES","Score":null,"Total":0}
CRMP2 and its phosphorylation prevent axonal misrouting of the corticospinal tract
During the development of the central nervous system (CNS), the formation of neural circuits such as the corticospinal tract (CST) is crucial to control voluntary movement and is regulated by axonal guidance mechanisms.
In this study, we examined the role of CRMP2 (Collapsin response mediator protein 2) in the formation of CST. CRMP2, which binds to actin and microtubules to control the cytoskeleton, is a phosphoprotein whose activity depends on its phosphorylated state. To inhibit Cyclin-dependent kinase 5 (Cdk5) phosphorylation, CRMP2 knock-in (crmp2ki/ki) mice were generated in which the serine residue at position 522 was replaced with alanine. Our results showed that both CRMP2 knock-out (crmp2-/-) and crmp2ki/ki mice exhibited higher percentages of CST axons that crossed the midline erroneously than wild-type (WT) mice. However, in mice lacking CRMP1, which is highly homologous to CRMP2, few axons crossed the midline, similar to WT mice. Additionally, crmp2-/- and crmp2ki/ki mice showed decreased proportions of independent forelimb movements. These findings emphasize that CRMP2 and its phosphorylation are necessary for proper CST formation in the mouse CNS.
期刊介绍:
Neuroscience Letters is devoted to the rapid publication of short, high-quality papers of interest to the broad community of neuroscientists. Only papers which will make a significant addition to the literature in the field will be published. Papers in all areas of neuroscience - molecular, cellular, developmental, systems, behavioral and cognitive, as well as computational - will be considered for publication. Submission of laboratory investigations that shed light on disease mechanisms is encouraged. Special Issues, edited by Guest Editors to cover new and rapidly-moving areas, will include invited mini-reviews. Occasional mini-reviews in especially timely areas will be considered for publication, without invitation, outside of Special Issues; these un-solicited mini-reviews can be submitted without invitation but must be of very high quality. Clinical studies will also be published if they provide new information about organization or actions of the nervous system, or provide new insights into the neurobiology of disease. NSL does not publish case reports.