Spinning the Matrix – Mechanisms of Basement Membrane Secretion and Assembly

Abstract

Basement membranes (BMs) are sheet‐like extracellular matrices that line the basal surfaces of epithelial tissues and surround muscles, adipose tissue, and nerves. My lab studies how regulated changes to BM architecture contribute to tissue morphogenesis. In Drosophila, elongation of the initially spherical egg chamber coincides with the generation of a polarized network of fibrils in its surrounding BM. We found that BM fibrils are assembled from newly synthesized proteins in the pericellular spaces between the egg chamber’s epithelial cells and undergo oriented insertion into the planar BM network by directed epithelial migration. We further found that a Rab10‐dependent secretion pathway ensures that a subset of new BM proteins exit the cell through a basal region of the lateral membrane for fibril formation. Rab10 recruits kinesin motors to BM secretory vesicles and transports them to this location on a polarized microtubule array. Finally, by manipulating Rab10 function, we showed for the first time that BM fibrils play an instructive role in egg chamber elongation. This work identifies a novel intracellular trafficking pathway for BM proteins and highlights how regulated protein secretion can synergize with tissue movement to build a polarized BM architecture that controls tissue shape.