Integrins mediate their unconventional, mechanical-stress-induced secretion via RhoA and PINCH inDrosophila

Abstract

During the epithelium remodelling such as the flattening of the Drosophila follicular epithelium, the α-integrin subunits are unconventionally secreted through a dGRASP-dependent route that is built de novo. The biogenetic process starts with the upregulation of a small subset of targeted mRNAs, including dgrasp. Here, we show that dgrasp mRNA upregulation is triggered by the tension of the underlying oocyte and by applied external forces at the basal side of the follicular epithelium. We show that integrins are also involved in dgrasp mRNA upregulation and the epithelium remodelling. Tension leads to the recruitment of RhoA to the plasma membrane, where it participates in its remodelling. The LIM protein PINCH can cycle to the nucleus and is involved in dgrasp mRNA upregulation. We propose that integrins are involved in triggering the biogenesis of their own unconventional secretion route that they use to strengthen adhesion and ensure epithelial integrity at the next stages of development, perhaps by acting as mechanosensors of the underlying tension through RhoA and PINCH.

Genetic Evidence for Antagonism Between Pak Protein Kinase and Rho1 Small GTPase Signaling in Regulation of the Actin Cytoskeleton During Drosophila Oogenesis

“…Recently, it was shown that the Rho1 actomyosin contractility pathway is required for this separation between follicle cells at the basal membrane and presumably this signaling is activated by RhoGEF2 (Schotman et al 2009). …”

Golgi Bypass: Skirting Around the Heart of Classical Secretion

“…Golgi bypass has also been observed in Drosophila follicular epithelial cells (Schotman et al 2008;Schotman et al 2009). During a key stage termed 10B in the development and growth of the egg chamber during oogenesis, the columnar epithelial cells that surround the oocyte are required to flatten to maintain their coverage.…”

Signalling to and from the secretory pathway

“…For instance, the expression of certain genes that encode proteins of the secretory pathway changes at specific stages of development in Drosophila melanogaster and zebrafish (Dunne et al, 2002;Schotman et al, 2009;Coutinho et al, 2004). Furthermore, the maturation of professional secretory cells, such as antibody-producing plasma cells (Iwakoshi et al, 2003), leads to an increase in ERES number and size, as well as Golgi volume (Farhan et al, 2008;Guo and Linstedt, 2006;Forster et al, 2006), thus rendering the cell competent to accommodate an increase in cargo load.…”