Several members of the ADAM (a disintegrin and metalloprotease) family of proteins have been implicated in biological processes ranging from fertilization to myoblast fusion and neural cell fate determination. These proteins have so far been studied mostly in terms of their protease activity, but a considerable amount of evidence suggests that many ADAMs are also important as receptors for cell-surface integrins. We have shown that, for one such member of the family, ADAM23, mRNA transcripts are expressed in neuronal cells throughout the rat brain, at all stages of postnatal development, and that particularly high transcript concentrations are found in the hippocampus and cerebellum. Using an antibody that we raised against the rat ADAM23 disintegrin domain, we found that ADAM23 is present at detectable levels only in nervous system tissue. Our analysis of ADAM23 expression in cultured cerebellar granule cells (CGCs) furthermore suggested that this protein is synthesized as a glycosylated precursor of about 100 kD whose maturation depends on cleavage by furin or a related enzyme. We have also shown ADAM23 to be expressed primarily as a cell-surface protein that appears to be localized to sites of intercellular contact. Taken together, these data are consistent with a model wherein ADAM23 serves to mediate cell-cell interactions within the mammalian CNS.
- Granule cell