Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P56851 (epididymal)
 11,273 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The members of the nectin/CD155 gene family represent a growing class of novel cell adhesion molecules of the immunoglobulin superfamily. In the present study, we describe the generation of a mouse line lacking a functional nectin-2 gene (nectin-2LacZ/LacZ) and analyze the resulting male-specific infertility phenotype. Although nectin-2LacZ/LacZ males produced normal amounts of motile spermatozoa, scanning electron microscopy revealed severe malformations of the spermatozoan head and midpiece. Besides a 4-fold reduction in migration of nectin-2LacZ/LacZ spermatozoa to the oviducts, in vitro binding to zona-intact mouse oocytes was reduced 6-fold. On the other hand, nectin-2LacZ/LacZ spermatozoa bound to zona-free hamster oocytes at near-wild type levels but, remarkably, failed to penetrate. In addition to the previously reported expression of nectin-2 and nectin-3 at Sertoli-spermatid junctions and of nectin-2 at inter-Sertoli cell junctions, we also found nectin-2 to localize at apical cell-cell junctions of the epididymal epithelium. Expression analysis of a LacZ knockin gene into the defunct nectin-2 gene in nectin-2LacZ/LacZ mice provided additional support for our earlier conjecture that in normal testis, nectin-2 is produced exclusively by Sertoli cells. Finally, we found Sertoli-spermatid junctions in nectin-2LacZ/LacZ mice to be virtually devoid of the actin-bundling protein espin, suggesting that ectoplasmic specializations fail to form in the absence of nectin-2. Our functional analyses indicate that the infertility phenotype of nectin-2-deficient male mice is caused by a combination of reduced migration to the oviduct, spermatozoa-zona binding, and sperm-oocyte fusion. We corroborate our previous description of a heterotypic adhesion complex between Sertoli cells and elongated spermatids that is maintained by nectin-2 and nectin-3, respectively.
 ...
PMID:Loss of nectin-2 at Sertoli-spermatid junctions leads to male infertility and correlates with severe spermatozoan head and midpiece malformation, impaired binding to the zona pellucida, and oocyte penetration. 1280 98

In the male reproductive organs of mammals, the formation of spermatozoa takes place during two successive phases: differentiation (in the testis) and maturation (in the epididymis). The first phase, spermiogenesis, relies on a unique adherens junction, the apical ectoplasmic specialization linking the epithelial Sertoli cells to immature differentiating spermatids. Vezatin is a transmembrane protein associated with adherens junctions and the actin cytoskeleton in most epithelial cells. We report here the expression profile of vezatin during spermatogenesis. Vezatin is exclusively expressed in haploid germ cells. Immunocytochemical and ultrastructural analyses showed that vezatin intimately coincides, temporally and spatially, with acrosome formation. While vezatin is a transmembrane protein associated with adherens junctions in many epithelial cells, it is not seen at the ectoplasmic specializations, neither at the basal nor at the apical sites, in the seminiferous epithelium. In particular, vezatin does not colocalize with espin and myosin VIIa, two molecular markers of the ectoplasmic specialization. In differentiating spermatids, ultrastructural data indicate that vezatin localizes in the acrosome. In epididymal sperm, vezatin localizes also to the outer acrosomal membrane. Considering its developmental and molecular characteristics, vezatin may be involved in the assembly/stability of this spermatic membrane.
 ...
PMID:Vezatin, a ubiquitous protein of adherens cell-cell junctions, is exclusively expressed in germ cells in mouse testis. 1737 51

Principal cells of the epididymis are the most prominent cell type and are noted for an apical cell surface studded with microvilli. The latter contain channel proteins that condition the microenvironment of epididymal lumen and promote sperm maturation; however, the regulation of the structure and integrity of microvilli is not well known. Espins are a family of proteins implicated in microvillar growth. The objectives of this study were to assess the regulation of espin in epididymal principal cells both in vitro and in vivo. Treatment of immortalized rat caput epididymal (RCE) cells with increasing doses of a homogenized testicular extract revealed a dose-dependent increase in the size of microvilli. Reverse transcriptase-polymerase chain reaction (RT-PCR) of adult rat epididymal RNA using espin-specific primers indicated the presence of a band at about 290 base pairs (bp) in all regions. Western blot analysis using affinity-purified espin antibody confirmed the presence of an approximately 110-kDa band in the epididymis, corresponding to espin isoform 1. In adult rats, immunocytochemistry revealed espin expression over principal cells. In orchidectomized rats, espin expression was significantly reduced, whereas ligation of the efferent ducts resulted in a decrease of espin expression but not to the extent of orchidectomy. The fact that espin expression was restored to control levels in orchidectomized rats supplemented with high levels of testosterone indicated that its expression was dependent on androgens and not on other lumicrine factors derived from the testis. Taken together, these data indicate that espin is expressed in the epididymis and is regulated by androgens.
 ...
PMID:Microvillar size and espin expression in principal cells of the adult rat epididymis are regulated by androgens. 1740 66