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CD46 (membrane cofactor protein of complement, measles virus receptor): structural and functional divergence among
1Department of Immunology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Higashinari-ku, Osaka 537, Japan.
Abstract:
Human CD46 was identified as a complement regulator and was later shown to be a measles virus receptor. The ubiquitous distribution profile of CD46 accounted for systemic measles infection and general protection of host tissue/organs from autologous complement. A similar ubiquitous distribution was observed for swine and simian CD46 homologues based upon subsequent cDNA cloning and Northern analysis, reinforcing the roles of CD46. In contrast, recent cDNA cloning and distribution analyses of murine and guinea-pig CD46 revealed the predominant expression of these rodent CD46 homologues in the testis, especially in mature testicular germ cells. These results do not support the established functions of human CD46 but support the hypothesis that CD46 on sperm serves as a fertilization-related adhesion molecule toward eggs. Here, we review the structure, function and distribution of human CD46 and discuss the possible differences between human CD46 and its homologues recently cloned from a variety of non-human primates and other animals.
Insights
CD46, a complement regulator and measles virus receptor in humans, shows varied expression in other species. Rodent CD46 primarily functions in the testis, suggesting a role in fertilization.
Area of Science:
- Immunology
- Virology
- Reproductive Biology
Background:
- Human CD46 acts as a complement regulator and measles virus receptor, with widespread tissue distribution.
- This ubiquitous expression explains systemic measles infection and host tissue protection from complement.
- Similar widespread distribution was noted for swine and simian CD46 homologues.
Purpose of the Study:
- To review the structure, function, and distribution of human CD46.
- To discuss potential differences between human CD46 and its homologues in non-human primates and other animals.
- To explore the novel hypothesis of CD46's role in fertilization.
Main Methods:
- cDNA cloning and Northern analysis were used to determine CD46 homologue distribution.
- Comparative analysis of CD46 expression patterns across species.
Main Results:
- Murine and guinea-pig CD46 homologues are predominantly expressed in the testis, particularly in mature germ cells.
- This contrasts with the ubiquitous expression seen in human, swine, and simian CD46.
- The testicular expression supports a role for rodent CD46 in fertilization.
Conclusions:
- CD46 exhibits species-specific expression patterns and functions.
- Rodent CD46's testicular localization suggests a role as a fertilization-related adhesion molecule.
- Further research is needed to fully understand the diverse roles of CD46 homologues.