Elron (extracellular Leucine-Rich Repeat only) proteins are known to have roles in synapse formation, axon guidance, and cell-cell adhesion. Here we describe distinct roles for the two transmembrane Elron proteins K07A12.2 and LET-4/SYM-5/C44H4.2 in C. elegans epithelial cells. Both K07A12.2 and
let-4 single mutants have lethal defects in embryonic elongation and excretory system function. In the low-penetrance embryonic phenotype, epidermal cell morphology appears normal until embryonic elongation, at which point epidermal lesions form. This suggests a role for K07A12.2 and LET-4 in the maintenance of epidermal cell integrity during the stress of elongation. Another transmembrane Elron, SYM-1, acts redundantly with LET-4 during elongation (Davies et al., 1999). Both K07A12.2 and LET-4 GFP fusion reporters localize to the apical face of epidermal cells during elongation, suggesting an interaction with the embryonic sheath. Individuals that do not have the embryonic elongation defect develop a lethal excretory system defect. In the excretory system defect phenotype, both K07A12.2 and
let-4 single mutants accumulate fluid in the excretory system and die as fluid-filled L1s. The excretory system includes three tandem unicellular epithelial tubes: the excretory canal cell, the duct cell, and the pore cell. Although both K07A12.2 and LET-4 are required for a functioning excretory system, each functions in a different aspect of the excretory system. K07A12.2 mutants lack a pore cell autojunction, though it is currently unknown whether it fails to form or is lost during development. This phenotype suggests a role for K07A12.2 in initial formation of the pore cell, or in maintenance of the tube shape. A failure of either process could explain the excretory system defect. In
let-4 mutants, the pore autojunction is unaffected, but the duct cell lumen becomes distorted and discontinuous just before hatch, indicating a role for LET-4 in lumen integrity. LET-4::GFP is localized to the luminal (apical) side of the duct cell, and may interact with the extracellular matrix inside the lumen of the duct and pore cells. This work suggests roles for Elron proteins in mediating interactions between epithelia and the apical extracellular matrix to help maintain cell shape and integrity. Davies AG, et al. (1999) Genetics 153, 117-134.