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J. Biol. Chem., Vol. 282, Issue 26, 18945-18952, June 29, 2007

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CatSper, a Novel Transmembrane Protein in the CatSper Channel Complex^*

Jin Liu, Jingsheng Xia, Kwang-Hyun Cho, David E. Clapham, and Dejian Ren¹

From the Department of Biology, University of Pennsylvania, Philadelphia, Pennsylvania 19104 and Howard Hughes Medical Institute, Enders 1309, Children's Hospital Boston, Boston, Massachusetts 02115

Four CatSper ion channel subunit genes (CatSpers 1-4) are required for sperm cell hyperactivation and male fertility. The four proteins assemble (presumably as a tetramer) to form a sperm-specific, alkalinization-activated Ca²⁺-selective channel. We set out to identify proteins associating with CatSper that might help explain its unique role in spermatozoa. Using a transgenic approach, a CatSper1 complex was purified from mouse testis that contained heat shock protein 70-2, a testis-specific chaperone, and CatSper, a novel protein with two putative transmembrane-spanning domains. Like the CatSper ion channel subunits, CatSper was restricted to testis and localized to the principal piece of the sperm tail. CatSper protein is absent in CatSper1^-/- sperm, suggesting that it is required for trafficking or formation of a stable channel complex. CatSper is the first identified auxiliary protein to the CatSper channel.

Received for publication, February 5, 2007 , and in revised form, April 26, 2007.

The nucleotide sequence(s) reported in this paper has been submitted to the GenBank^TM/EBI Data Bank with accession number(s) EF199807 [GenBank] .

^* This work was supported by grants from the NICHD, National Institutes of Health. 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 Biology, University of Pennsylvania, 415 S. University Ave. Philadelphia, PA 19104. Tel.: 215-898-9271; Fax: 215-898-8780; E-mail: dren{at}sas.upenn.edu.

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