a splice isoform of dnedd4, dnedd4-long, negatively regulates neuromuscular synaptogenesis and viability in drosophiladnedd4拼接异构体,dnedd4-long负调节神经肌肉突触发生和果蝇生存能力.pdfVIP

下载本文档

1
0
约 14页
2017-09-05 发布于上海
举报
版权申诉

a splice isoform of dnedd4, dnedd4-long, negatively regulates neuromuscular synaptogenesis and viability in drosophiladnedd4拼接异构体,dnedd4-long负调节神经肌肉突触发生和果蝇生存能力.pdf

1、本文档共14页，可阅读全部内容。
2、有哪些信誉好的足球投注网站（book118）网站文档一经付费（服务费），不意味着购买了该文档的版权，仅供个人/单位学习、研究之用，不得用于商业用途，未经授权，严禁复制、发行、汇编、翻译或者网络传播等，侵权必究。
3、本站所有内容均由合作方或网友上传，本站不对文档的完整性、权威性及其观点立场正确性做任何保证或承诺！文档内容仅供研究参考，付费前请自行鉴别。如您付费，意味着您自己接受本站规则且自行承担风险，本站不退款、不进行额外附加服务；查看《如何避免下载的几个坑》。如果您已付费下载过本站文档，您可以点击这里二次下载。
4、如文档侵犯商业秘密、侵犯著作权、侵犯人身权等，请点击“版权申诉”（推荐），也可以打举报电话：400-050-0827(电话支持时间：9:00-18:30)。
5、该文档为VIP文档，如果想要下载，成为VIP会员后，下载免费。
6、成为VIP后，下载本文档将扣除1次下载权益。下载后，不支持退款、换文档。如有疑问请联系我们。
7、成为VIP后，您将拥有八大权益，权益包括：VIP文档下载权益、阅读免打扰、文档格式转换、高级专利检索、专属身份标志、高级客服、多端互通、版权登记。
8、VIP文档为合作方或网友上传，每下载1次，网站将根据用户上传文档的质量评分、类型等，对文档贡献者给予高额补贴、流量扶持。如果你也想贡献VIP文档。上传文档

a splice isoform of dnedd4, dnedd4-long, negatively regulates neuromuscular synaptogenesis and viability in drosophiladnedd4拼接异构体,dnedd4-long负调节神经肌肉突触发生和果蝇生存能力

A Splice Isoform of DNedd4, DNedd4-Long, Negatively Regulates Neuromuscular Synaptogenesis and Viability in Drosophila Yunan Zhong1,3, Alina Shtineman-Kotler1,3, Leo Nguyen1,3, Konstantin G. Iliadi2,4, Gabrielle L. Boulianne2,4, Daniela Rotin1,3* 1 Program in Cell Biology, The Hospital for Sick Children, Toronto, Canada, 2 Program in Developmental and Stem Cell Biology, The Hospital for Sick Children, Toronto, Canada, 3 Department of Biochemistry, University of Toronto, Toronto, Canada, 4 Department of Molecular Genetics, University of Toronto, Toronto, Canada Abstract Background: Neuromuscular (NM) synaptogenesis is a tightly regulated process. We previously showed that in flies, Drosophila Nedd4 (dNedd4/dNedd4S) is required for proper NM synaptogenesis by promoting endocytosis of commissureless from the muscle surface, a pre-requisite step for muscle innervation. DNedd4 is an E3 ubiquitin ligase comprised of a C2-WW(x3)-Hect domain architecture, which includes several splice isoforms, the most prominent ones are dNedd4-short (dNedd4S) and dNedd4-long (dNedd4Lo). Methodology/Principal Findings: We show here that while dNedd4S is essential for NM synaptogenesis, the dNedd4Lo isoform inhibits this process and causes lethality. Our results reveal that unlike dNedd4S, dNedd4Lo cannot rescue the lethality of dNedd4 null (DNedd4T121FS) flies. Moreover, overexpression of UAS-dNedd4Lo specifically in wildtype muscles leads to NM synaptogenesis defects, impaired locomotion and larval lethality. These negative effects of dNedd4Lo are ameliorated by deletion of two regions (N-terminus and Middle region) unique to this isoform, and by inactivating the catalytic activity of dNedd4Lo, suggesting that these unique regions, as well as catalytic activity,