Abstract
The coxsackievirus and adenovirus receptor (CAR) is a transmembrane protein important for viral binding to target cells. Using RT-PCR, Western analysis, GST pull-down assay and indirect immunofluorescence, it was shown that CAR is expressed in male germ cells from mice, rats, and humans. CAR was detected in round spermatids in the testis as well as in purified, mature spermatozoa. The two membrane-bound isoforms of CAR occupied different subcellular sites in the acrosomal region of the spermatozoa. CAR was exposed on the surface of acrosome-reacted, but not acrosome-intact cells. Two CAR-binding proteins belonging to the ligand-of-numb protein-X (LNX) family also occupied distinct regions in spermatozoa. Finally, co-immunoprecipitation experiments demonstrated an interaction between CAR and JAM-C, a protein required for spermatid differentiation. Together, these findings imply a function for CAR in male fertility. The results also suggest that CAR in spermatozoa is inaccessible to adenovirus-based gene therapy vectors, and that the risk of germ line infection therefore is low.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Acrosome / metabolism
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Animals
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Antigens, Differentiation / metabolism*
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Carrier Proteins / metabolism
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Cell Adhesion Molecules / metabolism
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Cell Adhesion Molecules / physiology*
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Cell Differentiation / physiology
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Cells, Cultured
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Coxsackie and Adenovirus Receptor-Like Membrane Protein
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Epididymis / chemistry
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Epididymis / physiology
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Gene Expression Regulation*
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Humans
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Immunoglobulins / metabolism*
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In Vitro Techniques
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Intracellular Signaling Peptides and Proteins
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Male
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Membrane Proteins / metabolism*
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Mice
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Rats
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Rats, Sprague-Dawley
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Receptors, Virus / genetics
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Receptors, Virus / isolation & purification
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Receptors, Virus / metabolism*
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Recombinant Fusion Proteins / genetics
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Recombinant Fusion Proteins / metabolism
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Seminiferous Tubules / chemistry
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Seminiferous Tubules / cytology
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Seminiferous Tubules / physiology
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Spermatogenesis / genetics
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Spermatogenesis / physiology
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Spermatozoa / chemistry
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Spermatozoa / cytology
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Spermatozoa / physiology
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Testis / chemistry
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Testis / cytology*
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Testis / physiology
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Ubiquitin-Protein Ligases / metabolism
Substances
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Antigens, Differentiation
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CLMP protein, human
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CLMP protein, mouse
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Carrier Proteins
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Cell Adhesion Molecules
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Clmp protein, rat
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Coxsackie and Adenovirus Receptor-Like Membrane Protein
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Immunoglobulins
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Intracellular Signaling Peptides and Proteins
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Jam3 protein, mouse
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Lnx2 protein, mouse
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Membrane Proteins
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Receptors, Virus
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Recombinant Fusion Proteins
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Lnx1 protein, mouse
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Ubiquitin-Protein Ligases