Synaptopodin regulates spine plasticity: mediation by calcium stores
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Synaptopodin regulates spine plasticity: mediation by calcium stores. / Korkotian, Eduard; Frotscher, Michael; Segal, Menahem.
In: J NEUROSCI, Vol. 34, No. 35, 27.08.2014, p. 11641-51.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Synaptopodin regulates spine plasticity: mediation by calcium stores
AU - Korkotian, Eduard
AU - Frotscher, Michael
AU - Segal, Menahem
N1 - Copyright © 2014 the authors 0270-6474/14/3411641-11$15.00/0.
PY - 2014/8/27
Y1 - 2014/8/27
N2 - The role of synaptopodin (SP), an actin-binding protein residing in dendritic spines, in synaptic plasticity was studied in dissociated cultures of hippocampus taken from control and SP knock-out (SPKO) mice. Unlike controls, SPKO cultures were unable to express changes in network activity or morphological plasticity after intense activation of their NMDA receptors. SPKO neurons were transfected with SP-GFP, such that the only SP resident in these neurons is the fluorescent species. The localization and intensity of the transfected SP were similar to that of the native one. Because less than half of the spines in the transfected neurons contained SP, comparisons were made between SP-containing (SP(+)) and SP lacking (SP(-)) spines in the same dendritic segments. Synaptic plasticity was induced either in the entire network by facilitation of the activation of the NMDA receptor, or specifically by local flash photolysis of caged glutamate. After activation, spines that were endowed with SP puncta were much more likely to expand than SP(-) spines. The spine expansion was suppressed by thapsigargin, which disables calcium stores. The mechanism through which SP may promote plasticity is indicated by the observations that STIM-1, the sensor of calcium concentration in stores, and Orai-1, the calcium-induced calcium entry channel, are colocalized with SP, in the same dendritic spines. The structural basis of SP is likely to be the spine apparatus, found in control but not in SPKO cells. These results indicate that SP has an essential, calcium store-related role in regulating synaptic plasticity in cultured hippocampal neurons.
AB - The role of synaptopodin (SP), an actin-binding protein residing in dendritic spines, in synaptic plasticity was studied in dissociated cultures of hippocampus taken from control and SP knock-out (SPKO) mice. Unlike controls, SPKO cultures were unable to express changes in network activity or morphological plasticity after intense activation of their NMDA receptors. SPKO neurons were transfected with SP-GFP, such that the only SP resident in these neurons is the fluorescent species. The localization and intensity of the transfected SP were similar to that of the native one. Because less than half of the spines in the transfected neurons contained SP, comparisons were made between SP-containing (SP(+)) and SP lacking (SP(-)) spines in the same dendritic segments. Synaptic plasticity was induced either in the entire network by facilitation of the activation of the NMDA receptor, or specifically by local flash photolysis of caged glutamate. After activation, spines that were endowed with SP puncta were much more likely to expand than SP(-) spines. The spine expansion was suppressed by thapsigargin, which disables calcium stores. The mechanism through which SP may promote plasticity is indicated by the observations that STIM-1, the sensor of calcium concentration in stores, and Orai-1, the calcium-induced calcium entry channel, are colocalized with SP, in the same dendritic spines. The structural basis of SP is likely to be the spine apparatus, found in control but not in SPKO cells. These results indicate that SP has an essential, calcium store-related role in regulating synaptic plasticity in cultured hippocampal neurons.
KW - Animals
KW - Calcium
KW - Dendritic Spines
KW - Hippocampus
KW - Immunohistochemistry
KW - Mice
KW - Mice, Inbred C57BL
KW - Mice, Knockout
KW - Microfilament Proteins
KW - Microscopy, Confocal
KW - Neuronal Plasticity
KW - Patch-Clamp Techniques
KW - Synapses
KW - Transfection
U2 - 10.1523/JNEUROSCI.0381-14.2014
DO - 10.1523/JNEUROSCI.0381-14.2014
M3 - SCORING: Journal article
C2 - 25164660
VL - 34
SP - 11641
EP - 11651
JO - J NEUROSCI
JF - J NEUROSCI
SN - 0270-6474
IS - 35
ER -