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J. Biol. Chem., Vol. 279, Issue 2, 1224-1232, January 9, 2004

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Outer Dense Fibers Serve as a Functional Target for Cdk5·p35 in the Developing Sperm Tail^*

Jesusa L. Rosales, Byung-Chul Lee, Mohammad Modarressi, Krishna P. Sarker, Kyoung-Youl Lee, Young-Gil Jeong, Richard Oko, and Ki-Young Lee¶

From the Department of Cell Biology and Anatomy, Cancer Biology and Neuroscience Research Groups, The University of Calgary, Calgary, Alberta T2N 4N1, Canada and Department of Anatomy and Cell Biology, Queen's University, Kingston, Ontario K7L 3N6, Canada

Cdk5 is ubiquitously expressed in all tissues, but its activators, p35 and p39, are principally found in brain, and Cdk5 activity has mostly been associated with brain development, particularly neuronal differentiation and migration. Here we show that the p35 transcript and protein are also present in the testis, and an active Cdk5·p35 complex exists in this tissue as well. Cdk5 and p35 are prominently observed in elongating spermatid tails, particularly over the tail outer dense fibers (ODF). The appearance of Cdk5·p35 proceeds from the proximal to the distal end of elongating spermatids, coinciding with the proximal to distal assembly of ODF along the length of the tail axoneme. Incidentally, increased Cdk5·p35 activity is observed in isolated elongating spermatids and at a time when elongating spermatids appear in the developing testis, suggesting a role for Cdk5·p35 in spermiogenesis. The presence of Cdk5 and p35 in ODF isolated from rat sperm tails implies a strong association among these proteins. In vitro ODF phosphorylation by Cdk5·p35 and decreased in vivo sperm tail ODF phosphorylation in p35-deficient mice indicate that Cdk5·p35 is an integral component of ODF and that ODF is a functional Cdk5·p35 target in the testis. Our results demonstrate for the first time that Cdk5·p35 may participate in the regulation of sperm tail development via a mechanism involving ODF phosphorylation. Apparently, as in brain development, Cdk5·p35 plays a part in testis development.

Received for publication, October 2, 2003 , and in revised form, October 24, 2003.

^* This work was supported by grants from the Canadian Institutes of Health Research to R. O. and K.-Y. L., an Alberta Heritage Foundation for Medical Research Scholar. 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.

Current address: Dept. of Anatomy, College of Medicine, Konyang University, Nonsan, Chungnam 320-711, South Korea.

^¶ To whom correspondence should be addressed: Dept. of Cell Biology and Anatomy, Faculty of Medicine, The University of Calgary, 3330 Hospital Dr. N. W., Calgary, Alberta T2N 4N1, Canada. Tel.: 403-220-8723; Fax: 403-270-0834; E-mail: kylee{at}ucalgary.ca.

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