![]() ![]() Using a Spatc1l-knockout (KO) mice generated by CRISPR/Cas9 genome editing, we found that male mice lacking Spatc1l were completely sterile owing to separation of sperm heads from sperm tails. A proteomic analysis revealed that SPATC1L interacts with the regulatory (R) subunit of cAMP-dependent protein kinase (PKA) in male germ cells, discovering a new PKA-binding protein. Expression of SPATC1L started from spermatids and the protein was localized to the neck region in testicular sperm. ![]() In this study, we investigated the characteristics and functions of SPATC1L protein during male germ cell development. A further study using an antibody against SPATC1L generated using a Glutathione-S-transferase (GST)-fusion protein showed that SPATC1L is specifically expressed as a 38-kDa protein in spermatogenic cells 8. Spatc1l was predicted to encode a protein with 342 amino acids. It was found that the mouse Spatc1l gene is transcribed exclusively in spermatogenic cells starting from day 20 after birth, when round spermatids appear in the seminiferous tubules in mice 5, 7. The human ortholog of Spatc1l is located in a genomic region (chromosome 21q22.3) of conserved synteny between mice and humans. Spatc1l encompasses approximately an 8-kb region in mouse chromosome 10. The Spatc1l gene was named after a spermatogenesis and centriole associated 1 ( Spatc1) gene which encodes a sperm centrosome protein showing partial amino acid sequence homology (~50%) with a protein encoded by Spatc1l. One such recently identified gene is spermatogenesis and centriole associated 1 like ( Spatc1l) (UniGene ID Mm.45611 GenBank accession number NM_029661). Further analyses predicted that these genes are involved in diverse functions during spermatogenesis and fertilization. Previous systematic in silico analyses of the round spermatid UniGene library (Lib.6786) and in vitro studies have identified a number of genes that are specifically expressed in the testis 5. Understanding the molecular mechanisms underlying spermatogenesis is critical for diagnosing male infertility. Human infertility rates are currently high, and about half of such cases are caused by male infertility 4. ![]() This tightly regulated process constitutes a unique feature of male reproduction and is important for successful male germ cell development. The intrinsic program in particular involves germ cell- and/or stage-specific genes, and determines which genes are utilized and when the genes are expressed. The regulation of gene expression during spermatogenesis occurs at three levels: intrinsic, interactive, and extrinsic 3. The tight modulation of this developmental process suggests the expression of a highly organized network of genes. Haploid round spermatids undergo dramatic morphological changes to become highly specialized sperm through events of cellular elongation and nuclear condensation, a process termed spermiogenesis 1, 2. ![]() During spermatogenesis, spermatogonial stem cells undergo mitotic proliferation, and primary spermatocytes undergo meiotic division to produce spermatids. Spermatogenesis, the process of male germ cell development, is a tightly regulated series of events that occur in successive mitotic, meiotic, and postmeiotic phases. Taken together, our results implicate the SPATC1L-PKA complex in maintaining the stability of the sperm head-tail junction, thereby revealing a new molecular basis for sperm head-tail integrity. The lack of SPATC1L is associated with a reduction in PKA activity in testicular sperm, and we identify capping protein muscle Z-line beta as a candidate target of phosphorylation by PKA in testis. Disruption of Spatc1l in mice leads to male sterility owing to separation of sperm heads from tails. Using CRISPR/Cas9-mediated genome engineering, we generate mice lacking SPATC1L. Moreover, SPATC1L associates with the regulatory subunit of protein kinase A (PKA). We find that mouse SPATC1L localizes to the neck region in testicular sperm. Expression analyses show that SPATC1L is expressed in mouse and human testes. Here we investigate a novel germ cell-specific gene, Spatc1l (spermatogenesis and centriole associated 1 like). Spermatogenesis is a tightly regulated process involving germ cell-specific and germ cell-predominant genes. ![]()
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |