Opposing roles for lipocalins and a CD36 family scavenger receptor in apical extracellular matrix-dependent protection of narrow tube integrity

All exposed epithelial surfaces, including the walls of internal tubes, are lined by a lipid and glycoprotein-rich apical extracellular matrix (aECM) that helps shape and protect the apical domain. Secreted lipocalins are lipid transporters frequently found within apical compartments. We show that loss of the Caenorhabditis elegans lipocalin LPR-1 disrupts the assembly of another lipocalin, LPR-3, within the pre-cuticle aECM that protects and shapes the narrow excretory duct and pore tubes. Loss of SCAV-2, a CD36 family scavenger receptor, restored LPR-3 matrix localization and suppressed the tube shaping defects of lpr-1 and a subset of pre-cuticle mutants, but not lpr-3 mutants. SCAV-2 accumulates at duct and pore apical surfaces and functions locally within these tubes. These data demonstrate that LPR-1 and SCAV-2 have opposing effects on narrow tube integrity by altering the content and organization of the luminal aECM of the tube, possibly by acting as transporters of LPR-3 or an LPR-3 cofactor. These results have broadly relevant implications regarding the importance of lipocalins and scavenger receptors for aECM organization and integrity of the narrowest tubes in the body.