Published online before print November 30, 2007

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Copyright © 2007 American Society for Investigative Pathology
American Journal of Pathology, doi:10.2353/ajpath.2007.070261

Accepted for publication August 16, 2007.

Article

Loss of Partitioning-Defective-3/Isotype-Specific Interacting Protein (Par-3/ASIP) in the Elongating Spermatid of RA175 (IGSF4A/SynCAM)-Deficient Mice

Eriko Fujita^*, Yuko Tanabe^*, Tomonori Hirose, Michel Aurrand-Lions, Tadashi Kasahara, Beat A. Imhof, Shigeo Ohno, and Takashi Momoi^*@

From the Division of Differentiation and Development, Department of Inherited Metabolic Disorder,* National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan; the Department of Biochemistry, Kyoritsu University of Pharmacy, Tokyo, Japan; the Department of Molecular Biology, Yokohama City University Graduate School of Medical Science, Yokohama City University School of Medical Science, Yokohama, Japan; and the Department of Pathology and Immunology, University of Geneva, Geneva, Switzerland

^@ To whom correspondence should be addressed. E-mail: momoi{at}ncnp.go.jp.

	Abstract

IGSF4a/RA175/SynCAM (RA175) and junctional adhesion molecules (Jams) are members of the immunoglobulin superfamily with a PDZ-binding domain at their C termini. Deficiency of Ra175 (Ra175^-/-) as well as Jam-C deficiency (Jam-C^-/-) causes the defect of the spermatid differentiation, oligo-astheno-teratozoospermia. Ra175^-/- elongating spermatids fail to mature further, whereas Jam-C^-/- round spermatids lose cell polarity, and most of Jam-C^-/- elongated spermatids are completely lost. RA175 and Jam-C seem to have similar but distinct functional roles during spermatid differentiation. Here we show that the cell polarity protein Par-3 with PDZ domains, a binding partner of Jams, is one of the associated proteins of the cytoplasmic region of RA175 in testis. Par-3 and Jam-C are partly co-localized with RA175 in the elongating and elongated spermatids; their distributions overlapped with that of RA175 on the tips of the dorsal region of the head of the elongating spermatid (steps 9 to 12) in the wild type. In the Ra175^-/- elongating spermatid, Par-3 was absent, and Jam-C was absent or abnormally localized. The RA175 formed a ternary complex with Jam-C via interaction with Par-3. The lack of the ternary complex in the Ra175^-/- elongating spermatid may cause the defect of the specialized adhesion structures, resulting in the oligo-astheno-teratozoospermia.