14-3-3 Proteins Regulate Protein Kinase a Activity to Modulate Growth Cone Turning Responses

Overview

Journal J Neurosci

Specialty Neurology

Date 2010 Oct 22

PMID 20962227

Citations 27

Authors

Christopher B Kent

Tadayuki Shimada

Gino B Ferraro

Brigitte Ritter

Patricia T Yam

Peter S McPherson

Frederic Charron

Timothy E Kennedy

Alyson E Fournier

Affiliations

Soon will be listed here.

Abstract

Growth cones regulate the speed and direction of neuronal outgrowth during development and regeneration. How the growth cone spatially and temporally regulates signals from guidance cues is poorly understood. Through a proteomic analysis of purified growth cones we identified isoforms of the 14-3-3 family of adaptor proteins as major constituents of the growth cone. Disruption of 14-3-3 via the R18 antagonist or knockdown of individual 14-3-3 isoforms switches nerve growth factor- and myelin-associated glycoprotein-dependent repulsion to attraction in embryonic day 13 chick and postnatal day 5 rat DRG neurons. These effects are reminiscent of switching responses observed in response to elevated cAMP. Intriguingly, R18-dependent switching is blocked by inhibitors of protein kinase A (PKA), suggesting that 14-3-3 proteins regulate PKA. Consistently, 14-3-3 proteins interact with PKA and R18 activates PKA by dissociating its regulatory and catalytic subunits. Thus, 14-3-3 heterodimers regulate the PKA holoenzyme and this activity plays a critical role in modulating neuronal responses to repellent cues.

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