Feedback inhibition of actin on Rho mediates content release from large secretory vesicles

• Published in: The Journal of cell biology Vol. 217; no. 5; pp. 1815 - 1826
• Main Authors: Segal, Dagan, Zaritsky, Assaf, Schejter, Eyal D, Shilo, Ben-Zion
• Format: Journal Article
• Language: English
• Published: United States Rockefeller University Press 07.05.2018
• Subjects: Actin; Actins - metabolism; Actomyosin; Actomyosin - metabolism; Amides - pharmacology; Animals; Biochemistry; Cellular biology; Coating; Contraction; Depsipeptides - pharmacology; Dismantling; Drosophila melanogaster - drug effects; Drosophila melanogaster - metabolism; Drosophila Proteins - metabolism; Eukaryotes; Feedback inhibition; Feedback, Physiological; Fruit flies; Gene Knockdown Techniques; Glycoproteins; Homeostasis; Localization; Membranes; Models, Biological; Myosin; Negative feedback; Nucleation; Oscillations; Profilins - metabolism; Proteins; Pyridines - pharmacology; rho GTP-Binding Proteins - metabolism; Salivary gland; Salivary glands; Secretion; Secretory vesicles; Secretory Vesicles - drug effects; Secretory Vesicles - metabolism; Temporal variations; Vesicle fusion; Vesicles
• ISSN: 0021-9525; 1540-8140
• DOI: 10.1083/jcb.201711006

Secretion of adhesive glycoproteins to the lumen of larval salivary glands is performed by contraction of an actomyosin network assembled around large secretory vesicles, after their fusion to the apical membranes. We have identified a cycle of actin coat nucleation and disassembly that is independent of myosin. Recruitment of active Rho1 to the fused vesicle triggers activation of the formin Diaphanous and actin nucleation. This leads to actin-dependent localization of a RhoGAP protein that locally shuts off Rho1, promoting disassembly of the actin coat. When contraction of vesicles is blocked, the strict temporal order of the recruited elements generates repeated oscillations of actin coat formation and disassembly. Interestingly, different blocks to actin coat disassembly arrested vesicle contraction, indicating that actin turnover is an integral part of the actomyosin contraction cycle. The capacity of F-actin to trigger a negative feedback on its own production may be widely used to coordinate a succession of morphogenetic events or maintain homeostasis.