The F-Actin Binding Protein Cortactin Regulates the Dynamics of the Exocytotic Fusion Pore through its SH3 Domain

Frontiers in Cellular Neuroscience
Arlek M González-JamettAna M Cárdenas

Abstract

Upon cell stimulation, the network of cortical actin filaments is rearranged to facilitate the neurosecretory process. This actin rearrangement includes both disruption of the preexisting actin network and de novo actin polymerization. However, the mechanism by which a Ca(2+) signal elicits the formation of new actin filaments remains uncertain. Cortactin, an actin-binding protein that promotes actin polymerization in synergy with the nucleation promoting factor N-WASP, could play a key role in this mechanism. We addressed this hypothesis by analyzing de novo actin polymerization and exocytosis in bovine adrenal chromaffin cells expressing different cortactin or N-WASP domains, or cortactin mutants that fail to interact with proline-rich domain (PRD)-containing proteins, including N-WASP, or to be phosphorylated by Ca(2+)-dependent kinases, such as ERK1/2 and Src. Our results show that the activation of nicotinic receptors in chromaffin cells promotes cortactin translocation to the cell cortex, where it colocalizes with actin filaments. We further found that, in association with PRD-containing proteins, cortactin contributes to the Ca(2+)-dependent formation of F-actin, and regulates fusion pore dynamics and the number of exocy...Continue Reading

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Citations

Jun 7, 2018·Molecular Biology of the Cell·Agila Somasundaram, Justin W Taraska
Aug 31, 2017·Pflügers Archiv : European journal of physiology·Fernando D Marengo, Ana M Cárdenas
Jul 22, 2017·Pflügers Archiv : European journal of physiology·Luis M Gutiérrez, José Villanueva
Dec 22, 2019·International Journal of Molecular Sciences·Ximena Báez-MatusAna M Cárdenas
Dec 11, 2020·The Neuroscientist : a Review Journal Bringing Neurobiology, Neurology and Psychiatry·Jorge Arriagada-DiazArlek M Gonzalez-Jamett

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Methods Mentioned

BETA
confocal microscopy
transfection
transfections
GTPase

Software Mentioned

ImageJ
IGOR
PatchMaster
Image

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