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: 9507051
• 负责人: Tracy M. Clement
• 金额: $ 24.9万
• 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 2020-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9507051
• 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; imaging system; in vitro Assay; in vivo; innovation; insight; male; mutant mouse model; novel; protein complex; protein function; public health relevance; sperm cell; 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）：男性生育需要适当的精子发育。为了产生有能力进行施肥的精子，发育中的精子经历了细胞形状和结构的根本变化，但对于精子形态发生所需的遗传贡献和分子机制知之甚少。最近的证据明确指出，与肌动蛋白相关的蛋白质（如7B（ACTL7B））对于此过程至关重要。当前研究的果阿是定义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）功能的两种机制，并了解如何产生受精的精子。不育会影响大约十个与男性有关的病例中一半的夫妇，但是几乎一半的男性不育症病例是特发性，原因未知。这项研究将检验以下假设：ACTL7B在肌动蛋白细胞骨架的调节和组织中起作用，以实现精子形态发生和男性生育能力。将确定ACTL7B与蛋白质或蛋白质复合物的分子关联，将评估ACTL7B直接影响肌动蛋白丝组织和动力学的能力，并在睾丸epplants中研究F-肌动蛋白动力学在发育精子中的作用。这些研究将有助于理解与肌动蛋白相关的蛋白质功能，特别是ARP在精子发生中产生可行精子以使生命延续的作用。