Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10815690 | Cellular Signalling | 2012 | 8 Pages |
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)P3) 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)P3 metabolism and dendritic Ca2Â + 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)P3 signals and shorter Ins(1,4,5)P3-dependent Ca2Â + transients. At synapses of itpka deficient neurons the levels of Ins(1,4,5)P3-5-phosphatase (inpp5a) and sarcoplasmic/endoplasmic reticulum calcium ATPase pump-2b (serca2b) were increased, indicating that decreased duration of Ins(1,4,5)P3 and Ca2Â + 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 Ca2Â + transients at mature synapses.
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Authors
Sabine Windhorst, Daniel Minge, Robert Bähring, Svenja Hüser, Claudia Schob, Christine Blechner, Hong-Ying Lin, Georg W. Mayr, Stefan Kindler,