cAMP-dependent regulation of spinesin/TMPRSS5 gene expression in astrocytes

Spinesin/TMPRSS5 is a mosaic type serine protease that is predominantly expressed in the spinal cord. To identify the mechanism of spinesin expression, we investigated its expression in vivo and in vitro using several cell lines. Immunohistochemical and in situ hybridization analyses revealed that mouse spinesin (m-spinesin) was abundantly expressed in white matter astrocytes. Similarly, we confirmed abundant expression of m-spinesin in astrocyte cell lines. Then, we analyzed the expression of variant forms of m-spinesin in these cell lines. Interestingly, a transmembrane type (type 4) variant was expressed in neuroblastoma and astrocyte cell lines, whereas a cytoplasmic type (type 1) variant was specifically expressed in astrocyte cell lines. Furthermore, expression of both variants was up-regulated by dibutyryl-cAMP (dbcAMP) treatment only in astrocyte cell lines. We also analyzed the promoter region of the m-spinesin gene and revealed that the 5'-flanking region from base pairs -224 to -188 was essential for cAMP-dependent regulation of its transcription. These results indicate that m-spinesin is involved in the function of astrocytes in the spinal cord and that there may be astrocyte-specific regulation of its gene expression.