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J. Biol. Chem., Vol. 280, Issue 46, 38625-38630, November 18, 2005
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1
2
3
From the
Institut de Génétique Humaine CNRS UPR1142, 141 Rue de la Cardonille, 34396 Montpellier Cedex 5, France,
Genetics Program, Department of Medicine and Department of Genetics and Genomics, Boston University School of Medicine, Boston, Massachusetts 02118, and ¶Université de Nîmes, Place Gabriel Péri, 30021 Nîmes Cedex 01, France
In mammals, male sex determination is controlled by the SRY protein, which drives differentiation of the bipotential embryonic gonads into testes by activating the Sertoli cell differentiation program. The morphological effects of SRY are well documented; however, its molecular mechanism of action remains unknown. Moreover, SRY proteins display high sequence variability among mammalian species, which makes protein motifs difficult to delineate. We previously isolated SIP-1/NHERF2 as a human SRY-interacting protein. SIP-1/NHERF2, a PDZ protein, interacts with the C-terminal extremity of the human SRY protein. Here we showed that the interaction of SIP-1/NHERF2 and SRY via the SIP-1/NHERF2 PDZ1 domain is conserved in mice. However, the interaction occurs via a domain that is internal to the mouse SRY protein and involves a different recognition mechanism than human SRY. Furthermore, we show that mouse and human SRY induce nuclear accumulation of the SIP-1/NHERF2 protein in cultured cells. Finally, a transgenic mouse line expressing green fluorescent protein under the control of the mouse Sry promoter allowed us to show that SRY and SIP-1/NHERF2 are co-expressed in the nucleus of pre-Sertoli cells during testis determination. Taken together, our results suggested that the function of SIP-1/NHERF2 as an SRY cofactor during testis determination is conserved between human and mouse.
Received for publication, April 15, 2005 , and in revised form, September 15, 2005.
* This work was supported in part by the European Economic Community though the Fifth Framework Program Grant GLG2-CT-1999-00741 and by the "Association pour la Recherche Contre le Cancer" Grant ARC3481 (to B. B.-B.). 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 Recipient of a Ph.D. grant from the Ligue Départementale de l'Hérault Contre le cancer.
2 Recipient of a Ph.D. grant from the French Ministè re de la Recherche et de l'Enseignement Supérieur.
3 To whom correspondence should be addressed. E-mail: francis{at}igh.cnrs.fr.
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