Down-regulation of Drosophila Glutactin, a cholinesterase-like adhesion molecule of the basement membrane, impairs development, compromises adult function and shortens lifespan

Basement membranes (BM) play fundamental roles in morphogenesis and tissue maintenance in multicellular organisms. Glutactin is a BM protein that belongs to the Cholinesterase-Like Adhesion Molecules (CLAMs) protein family. In Drosophila embryos, Glutactin has been shown to outline internal organs and to play a role in synapse formation. Here, we report that Glutactin is broadly expressed in BM surrounding most vital tissues of the larva and the adult, and within the larval muscle sarcomere. Ubiquitous RNAi driven down-regulation of Glutactin expression (Tub>Glt-RNAi) resulted in pronounced impairments in larval and adult locomotor behavior, reduced oviposition, and shortened lifespan. Muscle-specific down-regulation of Glutactin resulted in reduced larval crawling speed indicating a secondary function for Glutactin independent of BM expression. Tub>Glt-RNAi pupa showed abdominal scars, suggestive of defects in histoblast nest expansion and replacement of larval epidermal cells, and a high mortality rate at eclosion. Surviving adults showed a range of morphological and physiological defects including excess melanization and pigmentation, incomplete rotation and duplication of the genitalia, and abnormal heart morphology and contraction. Insofar excess melanization is symptomatic of internal tissue damage, we propose that Glutactin is essential for the mechanical stabilization of the BM and for its ability to withstand internal stresses.