NMDA Receptor Activation Suppresses Microtubule Growth and Spine Entry

Lukas Kapitein, KW Yau, SM Gouveia, WA van der Zwan, PS Wulf, Nanda Keijzer, Jeroen Demmers, J Jaworski, Anna Akhmanova, CC Hoogenraad

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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.
Original languageUndefined/Unknown
Pages (from-to)8194-8209
Number of pages16
JournalJournal of Neuroscience
Issue number22
Publication statusPublished - 2011

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