Inositol-1,4,5-trisphosphate 3-kinase A regulates dendritic morphology and shapes synaptic Ca2+ transients.
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Inositol-1,4,5-trisphosphate 3-kinase A regulates dendritic morphology and shapes synaptic Ca2+ transients. / Windhorst, Sabine; Minge, Daniel; Bähring, Robert; Hüser, Svenja; Schob, Claudia; Blechner, Christine; Lin, Hongying; Mayr, Georg W.; Kindler, Stefan.
In: CELL SIGNAL, Vol. 24, No. 3, 3, 2012, p. 750-757.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Inositol-1,4,5-trisphosphate 3-kinase A regulates dendritic morphology and shapes synaptic Ca2+ transients.
AU - Windhorst, Sabine
AU - Minge, Daniel
AU - Bähring, Robert
AU - Hüser, Svenja
AU - Schob, Claudia
AU - Blechner, Christine
AU - Lin, Hongying
AU - Mayr, Georg W.
AU - Kindler, Stefan
PY - 2012
Y1 - 2012
N2 - Inositol-1,4,5-trisphosphate 3-kinase-A (itpka) accumulates in dendritic spines and seems to be critically involved in synaptic plasticity. The protein possesses two functional activities: it phosphorylates inositol-1,4,5-trisphosphate (Ins(1,4,5)P(3)) and regulates actin dynamics by its F-actin bundling activity. To assess the relevance of these activities for neuronal physiology, we examined the effects of altered itpka levels on cell morphology, Ins(1,4,5)P(3) metabolism and dendritic Ca(2+) signaling in hippocampal neurons. Overexpression of itpka increased the number of dendritic protrusions by 71% in immature primary neurons. In mature neurons, however, the effect of itpka overexpression on formation of dendritic spines was weaker and depletion of itpka did not alter spine density and synaptic contacts. In synaptosomes of mature neurons itpka loss resulted in decreased duration of Ins(1,4,5)P(3) signals and shorter Ins(1,4,5)P(3)-dependent Ca(2+) transients. At synapses of itpka deficient neurons the levels of Ins(1,4,5)P(3)-5-phosphatase (inpp5a) and sarcoplasmic/endoplasmic reticulum calcium ATPase pump-2b (serca2b) were increased, indicating that decreased duration of Ins(1,4,5)P(3) and Ca(2+) signals results from compensatory up-regulation of these proteins. Taken together, our data suggest a dual role for itpka. In developing neurons itpka has a morphogenic effect on dendrites, while the kinase appears to play a key role in shaping Ca(2+) transients at mature synapses.
AB - Inositol-1,4,5-trisphosphate 3-kinase-A (itpka) accumulates in dendritic spines and seems to be critically involved in synaptic plasticity. The protein possesses two functional activities: it phosphorylates inositol-1,4,5-trisphosphate (Ins(1,4,5)P(3)) and regulates actin dynamics by its F-actin bundling activity. To assess the relevance of these activities for neuronal physiology, we examined the effects of altered itpka levels on cell morphology, Ins(1,4,5)P(3) metabolism and dendritic Ca(2+) signaling in hippocampal neurons. Overexpression of itpka increased the number of dendritic protrusions by 71% in immature primary neurons. In mature neurons, however, the effect of itpka overexpression on formation of dendritic spines was weaker and depletion of itpka did not alter spine density and synaptic contacts. In synaptosomes of mature neurons itpka loss resulted in decreased duration of Ins(1,4,5)P(3) signals and shorter Ins(1,4,5)P(3)-dependent Ca(2+) transients. At synapses of itpka deficient neurons the levels of Ins(1,4,5)P(3)-5-phosphatase (inpp5a) and sarcoplasmic/endoplasmic reticulum calcium ATPase pump-2b (serca2b) were increased, indicating that decreased duration of Ins(1,4,5)P(3) and Ca(2+) signals results from compensatory up-regulation of these proteins. Taken together, our data suggest a dual role for itpka. In developing neurons itpka has a morphogenic effect on dendrites, while the kinase appears to play a key role in shaping Ca(2+) transients at mature synapses.
KW - Animals
KW - Cells, Cultured
KW - Mice
KW - Mice, Knockout
KW - Rats
KW - Transfection
KW - Calcium Signaling
KW - Calcium/metabolism
KW - Cerebellum/metabolism
KW - Dendritic Spines/enzymology
KW - Hippocampus/enzymology/metabolism
KW - Inositol 1,4,5-Trisphosphate/metabolism
KW - Neurons/cytology/enzymology
KW - Phosphoric Monoester Hydrolases/metabolism
KW - Phosphotransferases (Alcohol Group Acceptor)/genetics/metabolism
KW - Sarcoplasmic Reticulum Calcium-Transporting ATPases/metabolism
KW - Synaptosomes/metabolism
KW - Animals
KW - Cells, Cultured
KW - Mice
KW - Mice, Knockout
KW - Rats
KW - Transfection
KW - Calcium Signaling
KW - Calcium/metabolism
KW - Cerebellum/metabolism
KW - Dendritic Spines/enzymology
KW - Hippocampus/enzymology/metabolism
KW - Inositol 1,4,5-Trisphosphate/metabolism
KW - Neurons/cytology/enzymology
KW - Phosphoric Monoester Hydrolases/metabolism
KW - Phosphotransferases (Alcohol Group Acceptor)/genetics/metabolism
KW - Sarcoplasmic Reticulum Calcium-Transporting ATPases/metabolism
KW - Synaptosomes/metabolism
M3 - SCORING: Journal article
VL - 24
SP - 750
EP - 757
JO - CELL SIGNAL
JF - CELL SIGNAL
SN - 0898-6568
IS - 3
M1 - 3
ER -
