Actomyosin in secretion: How flies spit

Datum

15.02.2019

Zeit

11:00 - 12:00

Sprecher

Benny Shilo

Zugehörigkeit

Weizmann Institute of Science, Rehovot, Israel

Sprache

en

Hauptthema

Biologie

Andere Themen

Biologie

Host

Elisabeth Knust

Beschreibung

The small GTPase Rho governs actomyosin-based contractility in a wide variety of cellular settings, by the parallel induction of actin polymerization and of myosin II recruitment and activation. Regulation of Rho function is mediated by guanine exchange factors (GEFs) and GTPase activating proteins (GAPs), which stimulate and inhibit Rho activity, respectively. We have been exploring the dynamics and molecular design of this fundamental circuitry in the context of exocytosis. Specifically, we study secretion of “glue” proteins from the epithelium of the Drosophila salivary gland as a model system. Glue protein exocytosis is achieved via uncommonly large secretory vesicles (>5 um in diameter). Rho-mediated assembly and contraction of an actomyosin coat that forms around these vesicles upon their fusion with the apical cell membrane, is critical for release of the glue material into the gland lumen. We have identified RhoGEF2 as the activator of Rho in this setting. RhoGEF2 is recruited to the fused vesicles, and its function is essential for activation of Rho (as monitored with an active Rho sensor) on the vesicle surface, and for vesicle contraction. Interestingly, an actomyosin coat still forms around the vesicles following knockdown of RhoGEF2, likely generated by basal levels of Rho-GTP, which diffuse from the apical membrane following fusion. RhoGEF2 recruitment is actin dependent, implying an amplification mechanism for establishing a coat sufficiently robust to enable contraction. This process is counteracted by a dedicated RhoGAP, RhoGAP71E, which is also recruited by actin, and whose inhibitory function is also essential for vesicle contraction. Content release from the giant secretory vesicles thus appears to require a finely timed balance between Rho activation and inhibition. A major challenge is to determine how temporal order is maintained within this circuitry, particularly since actin appears to serve as a shared recruiting element of both activating and inhibiting factors.

Letztmalig verändert: 16.02.2019, 01:07:39