The three sorCS genes are differentially expressed and regulated by synaptic activity.

We have isolated the murine sorCS3 gene, a new member of the family of receptors containing a Vps10p-domain. Receptors of this family facilitate rapid endocytosis and are thought to be involved in intracellular sorting. SorCS3 and the highly homologous sorCS1 and sorCS2 genes were expressed in a combinatorial, mostly non-overlapping pattern in both the developing and mature central nervous system. During development, distribution and abundancy of their transcripts was regulated. Moreover, their expression was differentially influenced by neuronal activity in the hippocampus of adult mice. Although kainic acid-induced seizures had no effect on sorCS2 mRNA levels, they dramatically increased the expression of sorCS1 and sorCS3. The activity-dependent induction of sorCS1 expression required de novo protein synthesis, whereas that of sorCS3 did not. Our results imply that the three sorCS genes have diverse, but partly overlapping functions in the developing and mature central nervous system.