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Originally published In Press as doi:10.1074/jbc.M702268200 on April 17, 2007

J. Biol. Chem., Vol. 282, Issue 24, 17900-17907, June 15, 2007
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Identification of an ADAM2-ADAM3 Complex on the Surface of Mouse Testicular Germ Cells and Cauda Epididymal Sperm*

Hitoshi Nishimura{ddagger}, Diana G. Myles§, and Paul Primakoff{ddagger}1

From the {ddagger}Department of Cell Biology and Human Anatomy, School of Medicine and the §Section of Molecular and Cellular Biology, University of California, Davis, California 95618

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.


Received for publication, March 15, 2007

* This work was supported by National Institutes of Health Grants U54-29125 and HD-16580. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

1 To whom correspondence should be addressed: Dept. of Cell Biology and Human Anatomy, School of Medicine, University of California, One Shields Ave., Davis, CA 95618. Tel.: 530-754-9997; Fax: 530-752-3085; E-mail: pdprimakoff{at}ucdavis.edu.


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