Spatial targeting of type II protein kinase A to filopodia mediates the regulation of growth cone guidance by cAMP

Jianzhong Han, Liang Han, Priyanka Tiwari, Zhexing Wen, James Q. Zheng

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)101-111
Number of pages11
JournalJournal of Cell Biology
Volume176
Issue number1
DOIs
StatePublished - Jan 1 2007

ASJC Scopus subject areas

  • Cell Biology

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