Open Close
Reference
Citation
Yang, T., Terman, J.R. (2012). 14-3-3ε couples protein kinase A to semaphorin signaling and silences plexin RasGAP-mediated axonal repulsion.  Neuron 74(1): 108--121.
FlyBase ID
FBrf0218615
Publication Type
Research paper
Abstract

The biochemical means through which multiple signaling pathways are integrated in navigating axons is poorly understood. Semaphorins are among the largest families of axon guidance cues and utilize Plexin (Plex) receptors to exert repulsive effects on axon extension. However, Semaphorin repulsion can be silenced by other distinct cues and signaling cascades, raising questions of the logic underlying these events. We now uncover a simple biochemical switch that controls Semaphorin/Plexin repulsive guidance. Plexins are Ras/Rap family GTPase activating proteins (GAPs) and we find that the PlexA GAP domain is phosphorylated by the cAMP-dependent protein kinase (PKA). This PlexA phosphorylation generates a specific binding site for 14-3-3ε, a phospho-binding protein that we find to be necessary for axon guidance. These PKA-mediated Plexin-14-3-3ε interactions prevent PlexA from interacting with its Ras family GTPase substrate and antagonize Semaphorin repulsion. Our results indicate that these interactions switch repulsion to adhesion and identify a point of convergence for multiple guidance molecules.

PubMed ID
PubMed Central ID
PMC3857333 (PMC) (EuropePMC)
Related Publication(s)
Note

Regulating small G protein signaling to coordinate axon adhesion and repulsion.
Yang and Terman, 2013, Small Gtpases 4(1): 34--41 [FBrf0221097]

Associated Information
Comments
Associated Files
Other Information
Secondary IDs
    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    Neuron
    Title
    Neuron
    Publication Year
    1988-
    ISBN/ISSN
    0896-6273
    Data From Reference