Reference Report

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. (Export to RIS)
FlyBase ID	FBrf0218615
Publication Type	Research paper
PubMed ID	22500634
PubMed 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.
DOI	10.1016/j.neuron.2011.12.034
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]
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Secondary IDs
Language of Publication	English
Additional Languages of Abstract
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Parent Publication
Publication Type	Journal
Abbreviation	Neuron
Title	Neuron
Publication Year	1988-
ISBN/ISSN	0896-6273
Data from Reference
Alleles (19)
	14-3-3ε^18A2 14-3-3ε^j2B10 14-3-3ε^NP1301 14-3-3ε^{Scer\UAS.T:Zzzz\FLAG} if^Scer\UAS.cUa mew^Scer\UAS.cWa mys¹ nvy^PDFKG1 Pka-C1^DN plexA^{RA.Scer\UAS.T:Ivir\HA1} plexA^{SA.Scer\UAS.T:Ivir\HA1} plexA^{Scer\UAS.T:Ivir\HA1} plexA^{SE.Scer\UAS.T:Ivir\HA1} Ras64B^{Val14.Scer\UAS} Ras85D^V12.Scer\UAS Scer\GAL4^{14-3-3ε-NP1301} Scer\GAL4^elav.PU Scer\GAL4^how-24B Sema-1a^Scer\UAS.cYa
Constructs (9)
	P{UAS-14-3-3ε.FLAG} P{UAS-if.U} P{UAS-mew.W} P{UAS-plexA.HA} P{UAS-plexA.RA.HA} P{UAS-plexA.SA.HA} P{UAS-plexA.SE.HA} P{UAS-Ras64B.V14} P{UAS-Ras85D.V12}
Genes (15)
	14-3-3ε if mew Mical mys nvy Pka-C1 plexA plexB Ras64B Ras85D Scer\GAL4 Sema-1a T:Ivir\HA1 T:Zzzz\FLAG
Insertions (1)
	P{GawB}14-3-3ε^NP1301
Natural transposons (1)
	P-element