title: Inositol-1,4,5-trisphosphate 3-kinase A regulates dendritic morphology and shapes synaptic Ca2+ transients.
abstract: 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.
authors: Institute of Signal Transduction, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. s.windhorst@uke.uni-hamburg.de
authors: Sabine
authors: S
authors: Windhorst
authors: Daniel
authors: D
authors: Minge
authors: Robert
authors: R
authors: Bähring
authors: Svenja
authors: S
authors: Hüser
authors: Claudia
authors: C
authors: Schob
authors: Christine
authors: C
authors: Blechner
authors: Hong-Ying
authors: HY
authors: Lin
authors: Georg W
authors: GW
authors: Mayr
authors: Stefan
authors: S
authors: Kindler
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling; D002478:Cells, Cultured; D002531:Cerebellum / Q000378:metabolism; D049229:Dendritic Spines / Q000201:enzymology; D006624:Hippocampus / Q000201:enzymology / Q000378:metabolism; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D000072181:Inositol Polyphosphate 5-Phosphatases; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000166:cytology* / Q000201:enzymology*; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000378:metabolism; D013574:Synaptosomes / Q000378:metabolism; D014162:Transfection
chemical_list: D015544:Inositol 1,4,5-Trisphosphate; D017853:Phosphotransferases (Alcohol Group Acceptor); C051038:Inositol 1,4,5-trisphosphate 3-kinase; D010744:Phosphoric Monoester Hydrolases; D000072181:Inositol Polyphosphate 5-Phosphatases; C000606432:Inpp5a protein, mouse; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D002118:Calcium