title: NMDA receptor activation suppresses microtubule growth and spine entry.
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.
authors.affiliation: Cell Biology, Faculty of Science, Utrecht University, 3584CH Utrecht, The Netherlands.
authors.forename: Lukas C
authors.initials: LC
authors.lastname: Kapitein
authors.forename: Kah Wai
authors.initials: KW
authors.lastname: Yau
authors.forename: Susana Montenegro
authors.initials: SM
authors.lastname: Gouveia
authors.forename: Wouter A
authors.initials: WA
authors.lastname: van der Zwan
authors.forename: Phebe S
authors.initials: PS
authors.lastname: Wulf
authors.forename: Nanda
authors.initials: N
authors.lastname: Keijzer
authors.forename: Jeroen
authors.initials: J
authors.lastname: Demmers
authors.forename: Jacek
authors.initials: J
authors.lastname: Jaworski
authors.forename: Anna
authors.initials: A
authors.lastname: Akhmanova
authors.forename: Casper C
authors.initials: CC
authors.lastname: Hoogenraad
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D018929:Cell Culture Techniques; D049229:Dendritic Spines / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism / Q000502:physiology*; D036881:Long-Term Synaptic Depression / Q000502:physiology; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008870:Microtubules / Q000378:metabolism / Q000502:physiology*; D009474:Neurons / Q000166:cytology* / Q000378:metabolism / Q000502:physiology; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists / Q000502:physiology*
chemical_list: C489787:MAP2 protein, rat; C534832:Mapre3 protein, rat; D008869:Microtubule-Associated Proteins; C121001:NR2B NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate; D002118:Calcium