MUP-4 is a novel transmembrane protein with functions in epithelial cell adhesion in Caenorhabditis elegans

Tissue functions and mechanical coupling of cells must be integrated throug hout development. A striking example of this coupling is the interactions o f body wall muscle and hypodermal cells in Caenorhabditis elegans. These ti ssues are intimately associated in development and their interactions gener ate structures that provide a continuous mechanical link to transmit muscle forces across the hypodermis to the cuticle. Previously, we established th at mup-4 is essential in embryonic epithelial (hypodermal) morphogenesis an d maintenance of muscle position. Here, we report that mup-4 encodes a nove l transmembrane protein that is required for attachments between the apical epithelial surface and the cuticular matrix. Its extracellular domain incl udes epidermal growth factor-like repeats, a von Willebrand factor A domain , and two sea urchin enterokinase modules. Its intracellular domain is homo logous to filaggrin, an intermediate filament (IF)-associated protein that regulates IF compaction and that has not previously been reported as part o f a junctional complex. MUP-4 colocalizes with epithelial hemidesmosomes ov erlying body wall muscles, beginning at the time of embryonic cuticle matur ation, as well as with other sites of mechanical coupling. These findings s upport that MUP-4 is a junctional protein that functions in IF tethering, c ell-matrix adherence, and mechanical coupling of tissues.