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J Cell Biol 2007 Jan 01;1761:101-11. doi: 10.1083/jcb.200607128.
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Spatial targeting of type II protein kinase A to filopodia mediates the regulation of growth cone guidance by cAMP.

Han J , Han L , Tiwari P , Wen Z , Zheng JQ .

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.

PubMed ID: 17200417
PMC ID: PMC2063631
Article link: J Cell Biol
Grant support: [+]

Species referenced: Xenopus
Genes referenced: adcyap1 akap13 bdnf camk2g ctrl isyna1 mag npy4r ntf3 ppp1r1a ptpa tbx2
Morpholinos: ppp1r1a MO1

Article Images: [+] show captions
References [+] :
Alder, Overexpression of synaptophysin enhances neurotransmitter secretion at Xenopus neuromuscular synapses. 1995, Pubmed, Xenbase