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

描述(由申请人提供)：男性生育需要精子细胞的正常发育。为了产生能够受精的精子，发育中的精子细胞经历了细胞形状和结构的根本性变化，但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，肌动蛋白样蛋白7B(ACTL7B)，在这一过程中是至关重要的。本研究的目的是明确ACTL7B介导精子发生的机制，以便更好地了解肌动蛋白相关蛋白(ARP)的功能机制以及受精能力精子是如何产生的。大约10%的夫妇受到不孕不育的影响，其中一半的病例与男性有关，但近一半的男性不育病例是原因不明的特发性不孕症。这项研究将验证ACTL7B在调节和组织肌动蛋白细胞骨架以实现精子细胞形态发生和男性生育的假设。将确定ACTL7B与发育中的精子细胞内的蛋白质或蛋白质复合体的分子结合，评估ACTL7B直接影响肌动蛋白细丝组织和动力学的能力，并将在睾丸外植体中研究F-肌动蛋白动力学在发育精子细胞中的作用。这些研究将有助于了解肌动蛋白相关蛋白的功能，特别是Arps在精子发生中的作用，以产生健康永生的精子。

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.