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

说明（由申请人提供）：男性生育需要适当的精子发育。为了产生能够受精的精子，发育中的精子在细胞形状和结构上发生了根本性的变化，但对精子形态发生所需的遗传贡献和分子机制知之甚少。最近的证据表明，肌动蛋白相关蛋白actin like 7B （ACTL7B）对这一过程至关重要。本研究的目的是明确ACTL7B介导精子发生的机制，以更好地了解肌动蛋白相关蛋白（Actin Related Protein， ARP）功能的两种机制，并了解受精能力精子的产生方式。不孕症影响大约10%的夫妇，其中一半的病例与男性有关，然而，近一半的男性不孕症病例是特发性的，原因不明。本研究将验证ACTL7B在肌动蛋白细胞骨架的调控和组织中对功能性精细胞形态发生和男性生育能力的影响。将确定ACTL7B与发育中的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 -肌动蛋白动力学在发育中的作用。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在精子发生中产生可存活精子以健康延续生命的作用。

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.