About this item:

69 Views | 77 Downloads

Author Notes:

Correspondence to James Q. Zheng: zhengjq@umdnj.edu

We would like to thank Dr. Renping Zhou (Rutgers University, Piscataway, NJ) for his help on this project and Dr. Susan Taylor for providing recombinant PKA RII proteins.

Subjects:

Research Funding:

This research is supported by grants from NIH (NS036241) and the New Jersey Commission on Spinal Cord Research (NJCSCR; 04-3029-SCR) to J.Q. Zheng as well as a postdoctoral fellowship from NJCSCR to J. Han (grant 06-2918-SCR).

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Cell Biology
  • ADULT MAMMALIAN CNS
  • CYCLASE-ACTIVATING POLYPEPTIDE
  • AKAP SIGNALING COMPLEXES
  • AXON GUIDANCE
  • CYCLIC-AMP
  • SYNAPTIC PLASTICITY
  • ANCHORING PROTEINS
  • NEURITE OUTGROWTH
  • LONG-RANGE
  • REGENERATION

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

Tools:

Journal Title:

Journal of Cell Biology

Volume:

Volume 176, Number 1

Publisher:

, Pages 101-111

Type of Work:

Article | Final Publisher PDF

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.

Copyright information:

© The Rockefeller University Press.

This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License (http://creativecommons.org/licenses/by-nc-sa/4.0/).

Creative Commons License

Export to EndNote