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

Am J Pathol. 2007 Dec;171(6):1800-10. doi: 10.2353/ajpath.2007.070261. Epub 2007 Nov 30.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Animals
  • Asthenozoospermia / genetics
  • Cell Adhesion Molecule-1
  • Cell Adhesion Molecules / analysis
  • Cell Adhesion Molecules / deficiency*
  • Cell Adhesion Molecules / metabolism
  • Cell Cycle Proteins
  • Cell Differentiation / genetics*
  • Immunoglobulins / analysis
  • Immunoglobulins / genetics
  • Immunoglobulins / metabolism
  • Immunoglobulins / physiology*
  • Male
  • Membrane Proteins / analysis
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Membrane Proteins / physiology*
  • Mice
  • Mice, Knockout
  • Protein Isoforms / analysis
  • Protein Isoforms / deficiency
  • Spermatids / chemistry
  • Spermatids / cytology*
  • Spermatids / metabolism
  • Testis / chemistry
  • Testis / cytology*
  • Testis / metabolism
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / physiology*


  • Adaptor Proteins, Signal Transducing
  • Cadm1 protein, mouse
  • Cell Adhesion Molecule-1
  • Cell Adhesion Molecules
  • Cell Cycle Proteins
  • Immunoglobulins
  • Jam3 protein, mouse
  • Membrane Proteins
  • Pard3 protein, mouse
  • Protein Isoforms
  • Tumor Suppressor Proteins