Loss of partitioning-defective-3/isotype-specific interacting protein (par-3/ASIP) in the elongating spermatid of RA175 (IGSF4A/SynCAM)-deficient mice.
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.
National Institute of Neuroscience, National Center of Neurology and Psychiatry, Oawahigashi-machi 4-1-1, Kodaira, Tokyo 187-8502, Japan.
Eriko
E
Fujita
Yuko
Y
Tanabe
Tomonori
T
Hirose
Michel
M
Aurrand-Lions
Tadashi
T
Kasahara
Beat A
BA
Imhof
Shigeo
S
Ohno
Takashi
T
Momoi
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D053627:Asthenozoospermia / Q000235:genetics; D000075982:Cell Adhesion Molecule-1; D015815:Cell Adhesion Molecules / Q000032:analysis / Q000172:deficiency* / Q000378:metabolism; D018797:Cell Cycle Proteins; D002454:Cell Differentiation / Q000235:genetics*; D007136:Immunoglobulins / Q000032:analysis / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D008297:Male; D008565:Membrane Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D020033:Protein Isoforms / Q000032:analysis / Q000172:deficiency; D013087:Spermatids / Q000737:chemistry / Q000166:cytology* / Q000378:metabolism; D013737:Testis / Q000737:chemistry / Q000166:cytology* / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000502:physiology*
D048868:Adaptor Proteins, Signal Transducing; C498598:Cadm1 protein, mouse; D000075982:Cell Adhesion Molecule-1; D015815:Cell Adhesion Molecules; D018797:Cell Cycle Proteins; D007136:Immunoglobulins; C486723:Jam3 protein, mouse; D008565:Membrane Proteins; C115084:Pard3 protein, mouse; D020033:Protein Isoforms; D025521:Tumor Suppressor Proteins