title: FNDC3A is required for adhesion between spermatids and Sertoli cells.
abstract: Symplastic spermatids (sys) male mice are sterile due to a recessive mutation that causes defective adhesion between spermatids and Sertoli cells within the seminiferous epithelium. We show that the mutation in sys mice involves a deletion of 1.24 Mb of chromosome 14. Comparative genomic analysis suggests that this region contains only one gene, Fndc3a. A genetic complementation analysis using mice with a specific mutation within Fndc3a verifies that mutation of Fndc3a is the cause of male sterility in sys mice. Fndc3a is a member of a three-gene family in mice. Fndc3a, which is expressed in several tissues including testis, encodes a novel protein composed of a proline-rich amino-terminus, nine fibronectin type-III domains, and a hydrophobic carboxy-terminus. The proline-rich region of each family member contains conserved amino acids that include a PPGY consensus binding site for type I WW domain containing proteins. The hydrophobic carboxy-terminus is similar to that found in 'tail-anchored' proteins, integral membrane proteins that are localized to the cytosolic face of the endoplasmic reticulum. Immunohistochemical staining indicated that FNDC3A localizes to the acrosome of spermatids, as well as to Leydig cells in the mouse testis. Acrosomal localization of FNDC3A is observed in spermatids between step 2 and step 10 inclusive. In step 12 spermatids, FNDC3A is largely absent from the acrosomal region with immunostaining being localized to vesicular structures located within the cytoplasm of elongate spermatids. Models are presented for the function of FNDC3A in mediating spermatid-Sertoli adhesion during mouse spermatogenesis.
authors.affiliation: Department of Developmental and Cell Biology, University of California, Irvine, CA 92697-3940, USA.
authors.forename: Kevin L
authors.initials: KL
authors.lastname: Obholz
authors.forename: Arsen
authors.initials: A
authors.lastname: Akopyan
authors.forename: Katrina G
authors.initials: KG
authors.lastname: Waymire
authors.forename: Grant R
authors.initials: GR
authors.lastname: MacGregor
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D002448:Cell Adhesion; D002875:Chromosomes; D005353:Fibronectins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D017353:Gene Deletion; D005816:Genetic Complementation Test; D016678:Genome; D057927:Hydrophobic and Hydrophilic Interactions; D007248:Infertility, Male / Q000139:chemically induced; D007985:Leydig Cells / Q000378:metabolism; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008954:Models, Biological; D008969:Molecular Sequence Data; D011392:Proline / Q000235:genetics; D017386:Sequence Homology, Amino Acid; D012708:Sertoli Cells / Q000502:physiology*; D013087:Spermatids / Q000378:metabolism / Q000502:physiology*; D013737:Testis / Q000378:metabolism
chemical_list: C515317:FNDC3A protein, mouse; D005353:Fibronectins; D011392:Proline