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Loss of partitioning-defective-3/isotype-specific interacting protein (par-3/ASIP) in the elongating spermatid of RA175 (IGSF4A/SynCAM)-deficient mice

Fujita, Eriko
Tanabe, Yuko
Hirose, Tomonori
Kasahara, Tadashi
Ohno, Shigeo
Momoi, Takashi
Published in American Journal of Pathology. 2007, vol. 171, no. 6, p. 1800-1810
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.
Keywords AnimalsAsthenozoospermia/geneticsCell Adhesion Molecules/analysis/ deficiency/metabolismCell Differentiation/ geneticsImmunoglobulins/analysis/genetics/metabolism/ physiologyMaleMembrane Proteins/analysis/genetics/metabolism/ physiologyMiceMice, KnockoutProtein Isoforms/analysis/deficiencySpermatids/chemistry/ cytology/metabolismTestis/chemistry/ cytology/metabolismTumor Suppressor Proteins/genetics/ physiology
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PMID: 18055550
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