title: Synaptic regulation of microtubule dynamics in dendritic spines by calcium, F-actin, and drebrin.
abstract: Dendritic spines are actin-rich compartments that protrude from the microtubule-rich dendritic shafts of principal neurons. Spines contain receptors and postsynaptic machinery for receiving the majority of glutamatergic inputs. Recent studies have shown that microtubules polymerize from dendritic shafts into spines and that signaling through synaptic NMDA receptors regulates this process. However, the mechanisms regulating microtubule dynamics in dendrites and spines remain unclear. Here we show that in hippocampal neurons from male and female mice, the majority of microtubules enter spines from highly localized sites at the base of spines. These entries occur in response to synapse-specific calcium transients that promote microtubule entry into active spines. We further document that spine calcium transients promote local actin polymerization, and that F-actin is both necessary and sufficient for microtubule entry. Finally, we show that drebrin, a protein known to mediate interactions between F-actin and microtubules, acts as a positive regulator of microtubule entry into spines. Together these results establish for the first time the essential mechanisms regulating microtubule entry into spines and contribute importantly to our understanding of the role of microtubules in synaptic function and plasticity.
authors.affiliation: Neuroscience Training Program, Department of Neuroscience, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin 53706, Department of Physiology, Faculty of Science, Mahidol University, Bangkok 10400, Thailand, and Aix-Marseille University, Neurobiologie des Interactions Cellulaires et Neurophysiopathologie, 13385 Marseille, France.
authors.forename: Elliott B
authors.initials: EB
authors.lastname: Merriam
authors.forename: Matthew
authors.initials: M
authors.lastname: Millette
authors.forename: Derek C
authors.initials: DC
authors.lastname: Lumbard
authors.forename: Witchuda
authors.initials: W
authors.lastname: Saengsawang
authors.forename: Thomas
authors.initials: T
authors.lastname: Fothergill
authors.forename: Xindao
authors.initials: X
authors.lastname: Hu
authors.forename: Lotfi
authors.initials: L
authors.lastname: Ferhat
authors.forename: Erik W
authors.initials: EW
authors.lastname: Dent
mesh_terms: D000199:Actins / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000378:metabolism; D003712:Dendrites / Q000378:metabolism; D049229:Dendritic Spines / Q000378:metabolism*; D005260:Female; D006624:Hippocampus / Q000378:metabolism; D008297:Male; D051379:Mice; D008870:Microtubules / Q000378:metabolism*; D009473:Neuronal Plasticity / Q000502:physiology; D009474:Neurons / Q000378:metabolism; D009479:Neuropeptides / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism*
chemical_list: D000199:Actins; D009479:Neuropeptides; C053386:drebrins; D002118:Calcium