Mechanisms of a Novel Actin Related Protein in Male Gametes Ensuring Fertility

雄性配子中新型肌动蛋白相关蛋白确保生育力的机制

• 批准号: 9768489
• 负责人: Tracy M. Clement
• 金额: $ 18.67万
• 依托单位: TEXAS A&M AGRILIFE RESEARCH
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-08-01 至 2020-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9768489
• 关键词: APOBEC2 gene; Acrosome; Actin-Binding Protein; Actins; Address; Affect; Binding Proteins; Biochemical; Biogenesis; Biological Process; Cell Nucleus; Cell Shape; Cell physiology; Cells; Cellular Structures; Chromatin; Complex; Couples; Cytoplasm; Cytoskeleton; Defect; Development; Ensure; Exhibits; F-Actin; Fertility; Fertilization; Genetic; Genetic Materials; Germ Cells; Goals; Human; Image; Immunity; In Vitro; Infertility; Intracellular Transport; Kinetics; Label; Laboratories; Lead; Life; Link; Male Infertility; Mammals; Mediating; Meiosis; Methods; Microfilaments; Molecular; Morphogenesis; Multiprotein Complexes; Mus; Muscle; Myopathy; Neoplasm Metastasis; Nerve Degeneration; Oocytes; Organelles; Play; Process; Protein Biochemistry; Proteins; Regulation; Role; Sequence Homology; Somatic Cell; Sperm Motility; Spermatids; Spermatogenesis; Spermiogenesis; Structure; System; Testing; Testis; Tissue Culture Techniques; Tissues; Transgenic Mice; Work; base; cell growth regulation; defined contribution; idiopathic infertility; imaging system; in vitro Assay; in vivo; innovation; insight; male; male fertility; mutant mouse model; novel; protein complex; protein function; public health relevance; sperm cell; sperm viability; tissue preparation; tool

DESCRIPTION (provided by applicant): Proper spermatid development is required for male fertility. To produce sperm competent for fertilization, the developing spermatid undergoes radical changes in cell shape and structure, yet little is known about the genetic contributions and molecular mechanisms required for spermatid morphogenesis. Recent evidence makes clear that the actin related protein, Actin like 7B (ACTL7B), is critical for this process. The goa of the current study is to define the mechanism by which ACTL7B mediates spermiogenesis to better understand both mechanisms of Actin Related Protein (ARP) function and to understand how fertilization competent sperm are produced. Infertility affects approximately ten percent of couples with half of these cases linked to the male, however nearly half of the cases of male infertility are idiopathic with unknown causes. This study will test the hypothesis that ACTL7B plays a role in regulation and organization of the actin cytoskeleton for functional spermatid morphogenesis and male fertility. The molecular associations of ACTL7B with proteins or protein complexes within developing spermatids will be determined, the ability of ACTL7B to directly affect actin filament organization and dynamics will be assessed, and the role of F-actin dynamics in developing spermatids will be investigated in testis explants. These studies will aid in understanding of actin related protein functions and specifically the role of ARPs in spermatogenesis to produce viable sperm for healthy perpetuation of life.

描述（由申请人提供）：男性生育能力需要适当的精子细胞发育。为了产生具有受精能力的精子，发育中的精子细胞的细胞形状和结构发生了根本性的变化，但人们对精子细胞形态发生所需的遗传贡献和分子机制知之甚少。最近的证据表明，肌动蛋白相关蛋白，肌动蛋白样 7B (ACTL7B)，对于这一过程至关重要。本研究的目标是明确 ACTL7B 介导精子发生的机制，以更好地了解肌动蛋白相关蛋白 (ARP) 的功能机制，并了解具有受精能力的精子是如何产生的。不育症影响大约百分之十的夫妇，其中一半病例与男性有关，但近一半的男性不育病例是原因不明的特发性。这项研究将验证以下假设：ACTL7B 在肌动蛋白细胞骨架的调节和组织中发挥作用，从而实现功能性精子细胞形态发生和男性生育力。将确定 ACTL7B 与发育中精子细胞内蛋白质或蛋白质复合物的分子关联，评估 ACTL7B 直接影响肌动蛋白丝组织和动力学的能力，并在睾丸外植体中研究 F-肌动蛋白动力学在精子细胞发育中的作用。这些研究将有助于了解肌动蛋白相关的蛋白质功能，特别是 ARP 在精子发生中的作用，以产生可行的精子以实现健康的生命延续。