Synaptic regulation of microtubule dynamics in dendritic spines by calcium, F-actin, and drebrin

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 sh...

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Bibliographic Details
Published in:The Journal of neuroscience 2013-10, Vol.33 (42), p.16471-16482
Main Authors: Merriam, Elliott B, Millette, Matthew, Lumbard, Derek C, Saengsawang, Witchuda, Fothergill, Thomas, Hu, Xindao, Ferhat, Lotfi, Dent, Erik W
Format: Article
Language:English
Subjects:
Actins - metabolism
Animals
Calcium - metabolism
Cells, Cultured
Cytoskeleton - metabolism
Dendrites - metabolism
Dendritic Spines - metabolism
Female
Hippocampus - metabolism
Male
Mice
Microtubules - metabolism
Neuronal Plasticity - physiology
Neurons - metabolism
Neuropeptides - metabolism
Synapses - metabolism
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Summary: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.
ISSN:0270-6474
1529-2401
1529-2401
DOI:10.1523/jneurosci.0661-13.2013