THE CALCIUM SENSING RECEPTOR AND ITS ALTERNATIVELY SPLICED FORM IN KERATINOCYTE DIFFERENTIATION

We have recently reported the presence of the calcium sensing receptor (CaR) in keratinocytes and suggested that it signaled calcium-induced differentiation of these cells. cDNA clones encoding the full-length CaR were isolated from human keratinocytes. In addition, an alternativ ely spliced form that lacks exon 5, encoding a portion of the extracel lular domain, also was found. The in frame deletion of 231 nucleotides of exon 5 resulted in the loss of function of the CaR as measured by calcium-stimulated production of inositol phosphates when transfected into HEK293 cells or keratinocytes. This variant produced a smaller Ca R protein with an altered glycosylation pattern compared with the full -length CaR. Coexpression of the spliced variant with the full-length CaR reduced the function of the full-length CaR. The full-length CaR w as expressed in undifferentiated keratinocytes consistent with their g reater response to elevated extracellular calcium in terms of increase d intracellular free calcium and production of inositol phosphates. Th e full-length CaR decreased as the keratinocytes differentiated with a n increase in the ratio of the spliced variant to the full-length form . The relative proportions of these two forms of CaR may regulate the calcium responsiveness of keratinocytes during their differentiation.