MDGA1, an IgSF molecule containing a MAM domain, heterophilically associates with axon- and muscle-associated binding partners through distinct structural domains.

Molecules belonging to the immunoglobulin superfamily (IgSF) are reported to be involved in intercellular communication in the developing nervous system. We have identified a novel GPI-anchored IgSF molecule containing a MAM (meprin, A5 protein, PTPmu) domain, named MDGA1, by screening for genes that are expressed by subpopulations of cells in the embryonic chick spinal cord. MDGA1 is selectively expressed by brachial LMCm motor neurons, some populations of DRG neurons, and interneurons. We found that MDGA1 interacts heterophilically with axon-rich regions, mainly through its MAM domain. Interestingly, MDGA1 also interacts with differentiating muscle through its N-terminal region, which contains Ig domains. These results suggest that MDGA1 functions in MDGA1-expressing nerves en route to and at their target site.