CLCA splicing isoform associated with adhesion through β1-integrin and its scaffolding protein: specific expression in undifferentiated epithelial cells.

Jun Yamazaki, Kazuhiko Okamura, Kiyoko Uehara, Mitsutoki Hatta

The Journal of biological chemistry 2013 Feb 15

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We previously found that a rat CLCA homologue (rCLCA-f) modulates Ca(2+)-dependent Cl(-) transport in the ductal cells of the rat submandibular gland. CLCA proteins have been shown to be multifunctional, with roles in, for example, cell adhesion. Here, we describe the mRNA and protein expressions of a splicing isoform of rat rCLCA (rCLCA-t). This isoform is a 514-amino acid protein containing a C-terminal 59-amino acid that is distinct from the rCLCA-f sequence. Immunohistochemistry revealed rCLCA-t to be located in the basal cells of the rat submandibular gland excretory duct and the stratum basale of rat epidermis, whereas rCLCA-f was detected in cells during the process of differentiation. In a heterologous expression system, rCLCA-t was found to be a membrane protein present predominantly in the perinuclear region, and not to be either present on the cell surface or secreted. rCLCA-t failed to enhance ionomycin-induced Cl(-) conductance (unlike rCLCA-f). When compared with rCLCA-f, it weakened cell attachment to a greater extent and in a manner that was evidently modulated by intracellular Ca(2+), protein kinase C, and β(1)-integrin. rCLCA-t was found to associate with RACK1 (receptor for activated C kinase) and to reduce expression of mature β(1)-integrin. Treatment of rat skin with rCLCA-t siRNA increased the expression of β(1)-integrin in the stratum basale of the epidermis. These results are consistent with cell-specific splicing of rCLCA mRNA playing a role in the modulation of the adhesive potential of undifferentiated epithelial cells.

Citation

Jun Yamazaki, Kazuhiko Okamura, Kiyoko Uehara, Mitsutoki Hatta. CLCA splicing isoform associated with adhesion through β1-integrin and its scaffolding protein: specific expression in undifferentiated epithelial cells. The Journal of biological chemistry. 2013 Feb 15;288(7):4831-43