Wnt Regulates Axon Behavior through Changes in Microtubule Growth Directionality: A New Role for Adenomatous Polyposis Coli

Autor: Monica Hoyos-Flight, Eliza Siomou, Patricia C. Salinas, Lorenza Ciani, Silvia A. Purro, Eleanna Stamatakou
Rok vydání: 2008
Předmět:
Phosphoproteins/physiology
Time Factors
Dishevelled Proteins
Microtubules/*physiology
Microtubules
Mice
Ganglia
Spinal
Protein Isoforms
beta Catenin
Cells
Cultured
Mice
Knockout
Neuronal Plasticity
biology
General Neuroscience
Wnt signaling pathway
Adenomatous Polyposis Coli Protein/deficiency/*physiology
Protein Isoforms/physiology
beta Catenin/metabolism
Cell biology
Axons/*physiology
Wnt Proteins/*physiology
Signal Transduction
Adaptor Proteins
Signal Transducing/physiology
Beta-catenin
Adenomatous polyposis coli
Adenomatous Polyposis Coli Protein
Growth Cones
Down-Regulation
Transfection
Article
Wnt3 Protein
Microtubule
Down-Regulation/physiology
Wnt3A Protein
Animals
Ganglia
Spinal/cytology
Neurons
Afferent
Growth cone
Adaptor Proteins
Signal Transducing
Microtubule nucleation
Signal Transduction/physiology
Neuronal Plasticity/physiology
Phosphoproteins
Embryo
Mammalian
Axons
Wnt Proteins
Growth Cones/metabolism/physiology
Neurons
Afferent/physiology
Animals
Newborn
biology.protein
Axon guidance
Zdroj: The Journal of Neuroscience. 28:8644-8654
ISSN: 1529-2401
0270-6474
DOI: 10.1523/jneurosci.2320-08.2008
Popis: Axon guidance and target-derived signals control axonal behavior by regulating the cytoskeleton through poorly defined mechanisms. In particular, how these signaling molecules regulate the growth and directionality of microtubules is not well understood. Here we examine the effect of Wnts on growth cone remodeling, a process that precedes synapse formation. Time-lapse recordings reveal that Wnt3a rapidly inhibits growth cone translocation while inducing growth cone enlargement. These changes in axonal behavior are associated with changes in the organization of microtubules. Time-lapse imaging of EB3-GFP (green fluorescent protein)-labeled microtubule plus-ends demonstrates that Wnt3a regulates microtubule directionality, resulting in microtubule looping, growth cone pausing, and remodeling. Analyses of Dishevelled-1 (Dvl1) mutant neurons demonstrate that Dvl1 is required for Wnt-mediated microtubule reorganization and axon remodeling. Wnt signaling directly affects the microtubule cytoskeleton by unexpectedly inducing adenomatous polyposis coli (APC) loss from microtubule plus-ends. Consistently, short hairpin RNA knockdown of APC mimics Wnt3a function. Together, our findings define APC as a key Wnt signaling target in the regulation of microtubule growth direction.
Databáze: OpenAIRE
Externí odkaz: