Dynamic microtubules regulate dendritic spine morphology and synaptic plasticity.
By J. Jaworski, Lukas C. Kapitein, S. Gouveia, B. Dortland, Phebe S. Wulf, I. Grigoriev, Paola Camera, S. Spangler, P. D. Stefano, Jeroen A. A. Demmers and 4 more. Neuron, 2009
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Dendritic spines are the major sites of excitatory synaptic input, and their morphological changes have been linked to learning and memory processes. Here, we report that growing microtubule plus ends decorated by the microtubule tip-tracking protein EB3 enter spines and can modulate spine morphology. We describe p140Cap/SNIP, a regulator of Src tyrosine kinase, as an EB3 interacting partner that is predominantly localized to spines and enriched in the postsynaptic density. Inhibition of microtubule dynamics, or knockdown of either EB3 or p140Cap, modulates spine shape via regulation of the actin cytoskeleton. Fluorescence recovery after photobleaching revealed that EB3-binding is required for p140Cap accumulation within spines. In addition, we found that p140Cap interacts with Src substrate and F-actin-binding protein cortactin. We propose that EB3-labeled growing microtubule ends regulate the localization of p140Cap, control cortactin function, and modulate actin dynamics within dendritic spines, thus linking dynamic microtubules to spine changes and synaptic plasticity.
Subfields: Cell Biology, Cellular and Molecular Neuroscience
View Paper: https://www.semanticscholar.org/paper/4c7b011edc81140ddd96162c62d90acc8be9a107
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Citations in the corpus
- Branching out: mechanisms of dendritic arborization (2010, background): “Third, dendrites need to have the flexibility for adjustment in development and in response to experience — as indicated, for example, by dynamic microtubule invasion of spine”
- Tau mislocalization to dendritic spines mediates synaptic dysfunction independently of neurodegeneration (2010, methodology): “…per group. t test (B), ANOVA followed by Bonferroni post hoc analysis (D), *p < 0.05, ***p < 0.001. dynamicmicrotubules can ‘‘invade’’ dendritic spines to influence spine plasticity (Gu et al., 2008; Hu et al., 2008; Jaworski et al., 2009), potentially transporting bound tau into the spines.”
- An EB1-binding motif acts as a microtubule tip localization signal. (2009, neutral): “described ( Honnappa et al., 2005, 2006; Weisbrich et al., 2007).”