Identification of an ADAM2-ADAM3 complex on the surface of mouse testicular germ cells and cauda epididymal sperm.
Male mice lacking ADAM2 (fertilin beta) or ADAM3 (cyritestin) are infertile; cauda epididymal sperm (mature sperm) from these mutant mice cannot bind to the egg zona pellucida. ADAM3 is barely present in Adam2-null sperm, despite normal levels of this protein in Adam2-null testicular germ cells (TGCs; sperm precursor cells). Here, we have explored the molecular basis for the loss of ADAM3 in Adam2-null TGCs to clarify the biosynthetic and functional linkage of ADAM2 and ADAM3. A small portion of total ADAM3 was found present on the surface of wild-type and Adam2(-/-) TGCs at similar levels. In the Adam2-null TGCs, however, surface-localized ADAM3 exhibited an increased amount of an endoglycosidase H-resistant form that may be related to instability of ADAM3. Moreover, we found a complex between ADAM2 and ADAM3 on the surface of TGCs and sperm. The intracellular chaperone calnexin was a component of the testicular ADAM2-ADAM3 complex. Our findings suggest that the association with ADAM2 is a key element for stability of ADAM3 in epididymal sperm. The presence of the ADAM2-ADAM3 complex in sperm also suggests a potential role of ADAM2 with ADAM3 in sperm binding to the egg zona pellucida.
Nishimura
Hitoshi
H
Department of Cell Biology and Human Anatomy, School of Medicine, University of California, Davis, California 95618, USA.
Myles
Diana G
DG
Primakoff
Paul
P
D051722:ADAM Proteins / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism*; D004822:Epididymis / Q000166:cytology*; D000072196:Fertilins; D005854:Germ Cells / Q000166:cytology / Q000378:metabolism*; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D046912:Multiprotein Complexes; D013094:Spermatozoa / Q000166:cytology / Q000378:metabolism*; D013347:Subcellular Fractions; D013737:Testis / Q000166:cytology*
D008562:Membrane Glycoproteins; D046912:Multiprotein Complexes; D051722:ADAM Proteins; C000606454:ADAM2 protein, human; C000606458:Adam2 protein, mouse; C485429:Adam3 protein, mouse; D000072196:Fertilins