CLCA Splicing Isoform Associated with Adhesion through β1-Integrin and Its Scaffolding Protein

Background: CLCA family members have been shown to be multifunctional proteins. Results: A rat splicing isoform was localized to the stratum basale of the epidermis. This isoform was found to alter β1-integrin expression and cell adhesion. Conclusion: This isoform may modulate the adhesive potential of undifferentiated epithelial cells. Significance: Cell-specific splicing might confer a novel function on the epithelium. We previously found that a rat CLCA homologue (rCLCA-f) modulates Ca2+-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 Ca2+, protein kinase C, and β1-integrin. rCLCA-t was found to associate with RACK1 (receptor for activated C kinase) and to reduce expression of mature β1-integrin. Treatment of rat skin with rCLCA-t siRNA increased the expression of β1-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.

• Publication year

  2013

• Venue

  Journal of Biological Chemistry

• Publication date

  2013-01-07

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1074/jbc.M112.396481PMID 23297403PMCID PMC3576088
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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