Tetraspanin protein (TSP-15) integrity is required for epidermal integrity in Caenorhabditis elegans

Epidermal integrity is essential for animal development and survival. Here, we demonstrate that TSP-15, a member of the tetraspanin protein family, is required for epithelial membrane integrity in Caenorhabditis elegans. Reduction of tsp-15 function by mutation or by RNA interference elicits abnormalities of the hypodermis, including dissociation of the cuticle and degeneration of the hypodermis. Lethality during molting often results. Examination of GFP transgenic animals, genetic mosaic analysis and rescue assays revealed that TSP-15 functions in hyp7, a large syncytium that composes most of the hypodermis. Assays with a membrane-impermeable dye or leakage analysis of a hypodermal-specific marker indicate that the barrier function of the hypodermal membrane is impaired owing to the loss or reduction of TSP-15. These results indicate that TSP-15 functions in the maintenance of epithelial cell integrity.