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- Title
NMDA Receptor Activation Suppresses Microtubule Growth and Spine Entry.
- Authors
Kapitein, Lukas C.; Yau, Kah Wai; Gouveia, Susana Montenegro; van der Zwan, Wouter A.; Wulf, Phebe S.; Keijzer, Nanda; Demmers, Jeroen; Jaworski, Jacek; Akhmanova, Anna; Hoogenraad, Casper C.
- Abstract
Dynamic microtubules are important to maintain neuronal morphology and function, but whether neuronal activity affects the organization of dynamic microtubules is unknown. Here, we show that a protocol to induce NMDA-dependent long-term depression (LTD) rapidly attenuates microtubule dynamics in primary rat hippocampal neurons, removing the microtubule-binding protein EB3 from the growing microtubule plus-ends in dendrites. This effect requires the entry of calcium and is mediated by activation of NR2B-containing NMDA-type glutamate receptor. The rapid NMDA effect is followed by a second, more prolonged response, during which EB3 accumulates along MAP2-positive microtubule bundles in the dendritic shaft. MAP2 is both required and sufficient for this activity-dependent redistribution of EB3. Importantly, NMDA receptor activation suppresses microtubule entry in dendritic spines, whereas overexpression of EB3-GFP prevents NMDA-induced spine shrinkage. These results suggest that short-lasting and long-lasting changes in dendritic microtubule dynamics are important determinants for NMDA-induced LTD.
- Publication
Journal of Neuroscience, 2011, Vol 31, Issue 22, p8194
- ISSN
0270-6474
- Publication type
Article
- DOI
10.1523/JNEUROSCI.6215-10.2011