Spatial Targeting of Type II Protein Kinase A to Filopodia Mediates the Regulation of Growth Cone Guidance by CAMP

Overview

Journal J Cell Biol

Specialty Cell Biology

Date 2007 Jan 4

PMID 17200417

Citations 18

Authors

Jianzhong Han

Liang Han

Priyanka Tiwari

Zhexing Wen

James Q Zheng

Affiliations

Soon will be listed here.

Abstract

The second messenger cyclic adenosine monophosphate (cAMP) plays a pivotal role in axonal growth and guidance, but its downstream mechanisms remain elusive. In this study, we report that type II protein kinase A (PKA) is highly enriched in growth cone filopodia, and this spatial localization enables the coupling of cAMP signaling to its specific effectors to regulate guidance responses. Disrupting the localization of PKA to filopodia impairs cAMP-mediated growth cone attraction and prevents the switching of repulsive responses to attraction by elevated cAMP. Our data further show that PKA targets protein phosphatase-1 (PP1) through the phosphorylation of a regulatory protein inhibitor-1 (I-1) to promote growth cone attraction. Finally, we find that I-1 and PP1 mediate growth cone repulsion induced by myelin-associated glycoprotein. These findings demonstrate that the spatial localization of type II PKA to growth cone filopodia plays an important role in the regulation of growth cone motility and guidance by cAMP.

Citing Articles

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A critical role for STIM1 in filopodial calcium entry and axon guidance.

Shim S, Zheng J, Ming G Mol Brain. 2013; 6:51.

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