Two functionally diverse gamma tubulin core complexes

两种功能多样的伽马微管蛋白核心复合物

• 批准号: 9813115
• 负责人: TIMOTHY L MEGRAW
• 金额: $ 46.2万
• 依托单位: FLORIDA STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-08-01 至 2022-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9813115
• 关键词: Animals; Biochemical; Cell physiology; Cells; Centrosome; Complex; Data; Development; Developmental Process; Drosophila genus; Dwarfism; Eukaryota; FOLH1 gene; Family; Foundations; GTP-Binding Protein alpha Subunits, Gs; Genes; Goals; Hereditary Disease; Hybrids; Location; Measures; Meiosis; Microcephaly; Microtubule Stabilization; Microtubule-Organizing Center; Microtubules; Minus End of the Microtubule; Molecular; Mutation; N-terminal; Names; Organism; Orthologous Gene; Outcome; Plus End of the Microtubule; Polymers; Property; Protein Complex Subunit; Proteins; Regulation; Role; Side; Sperm Motility; Sperm Tail; Spermatogenesis; Spermiogenesis; Structure; Syndrome; Testing; Testis; Tissues; Transmission Electron Microscopy; Tubulin; Variant; Vesicle; catalyst; cell motility; cell type; gamma Tubulin; in vivo; novel; paralogous gene; protein complex; sperm cell; trafficking

Centrosomes are the major and best-understood microtubule-organizing centers (MTOCs) in animal cells. Mutations in genes that encode key centrosomal proteins impact developmental processes leading to syndromic microcephaly, primordial dwarfisms, and other inherited disorders. A major regulator of microtubules at centrosomes and other MTOCs is -tubulin, a highly conserved and tubulin variant that is specialized in catalyzing the initiation of microtubule polymer assembly. -tubulin associates with gamma tubulin complex proteins (GCPs) to form a ring complex (-TuRC). We found two distinct types of -TuRCs in Drosophila testis: the conventional one that is essential throughout the organism, and a second uncharacterized one whose unique GCP subunits are expressed in late stage testis and are required for sperm motility. This is the first known case of diversity of -TuRC core complexes in one organism. We propose to determine the subunit composition of the new testis-specific -TuRC and determine if it can assemble hybrid -TuRCs with the conventional GCP proteins. We will ascertain the MT nucleation properties of both -TuRCs and determine the role for the novel testis-specific variant in sperm motility. The outcomes of this project will be a new understanding of the functions of this essential MT nucleator complex biochemically and in vivo.

中心体是微管组织的主要和最好的理解中心 （MTOC）在动物细胞中的作用。编码关键中心体的基因突变 蛋白质影响导致综合征性小头畸形的发育过程， 原始侏儒症和其他遗传性疾病的主要调节剂 微管中心体和其他MTOC是微管蛋白，一个高度保守的 和微管蛋白变体，其专门催化微管的起始， 聚合物组装β-微管蛋白与γ-微管蛋白复合物蛋白缔合 （GCPs）形成环复合物（B-TuRC）。我们发现了两种不同类型的 在果蝇的睾丸中：在整个生殖过程中， 第二个未表征的，其独特的GCP亚基是 在晚期睾丸中表达，并且是精子运动所必需的。这是第一 一种生物体中β-TuRC核心复合物多样性的已知案例。我们提出 以确定新睾丸特异性EST-TuRC的亚基组成， 确定它是否可以与常规GCP蛋白组装杂交的EST-TuRC。 我们将确定两种α-TuRC的MT成核性质，并确定 新型睾丸特异性变体在精子活力中的作用。的成果 该项目将使人们对这一重要的MT的功能有一个新的认识 成核剂复合物生物化学和体内。