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Blechner, C.* ; Becker, L. ; Fuchs, H. ; Rathkolb, B. ; Prehn, C. ; Adler, T. ; Calzada-Wack, J. ; Garrett, L. ; Gailus-Durner, V. ; Morellini, F.* ; Conrad, S.* ; Hölter, S.M. ; Wolf, E.* ; Klopstock, T.* ; Adamski, J. ; Busch, D.* ; Hrabě de Angelis, M. ; Schmeisser, M.J.* ; Windhorst, S.*

Physiological relevance of the neuronal isoform of inositol-1,4,5-trisphosphate 3-kinases in mice.

Neurosci. Lett. 735:135206 (2020)
DOI
Open Access Green as soon as Postprint is submitted to ZB.
Inositol-1,4,5-trisphosphate 3-kinase-A (ITPKA) is the neuronal isoform of ITPKs and exhibits both actin bundling and InsP3kinase activity. In addition to neurons, ITPKA is ectopically expressed in tumor cells, where its oncogenic activity increases tumor cell malignancy. In order to analyze the physiological relevance of ITPKA, here we performed a broad phenotypic screening of itpka deficient mice. Our data show that among the neurobehavioral tests analyzed, itpka deficient mice reacted faster to a hotplate, prepulse inhibition was impaired and the accelerating rotarod test showed decreased latency of itpka deficient mice to fall. These data indicate that ITPKA is involved in the regulation of nociceptive pathways, sensorimotor gating and motor learning. Analysis of extracerebral functions in control and itpka deficient mice revealed significantly reduced glucose, lactate, and triglyceride plasma concentrations in itpka deficient mice. Based on this finding, expression of ITPKA was analyzed in extracerebral tissues and the highest level was found in the small intestine. However, functional studies on CaCo-2 control and ITPKA depleted cells showed that glucose, as well as triglyceride uptake, were not significantly different between the cell lines. Altogether, these data show that ITPKA exhibits distinct functions in the central nervous system and reveal an involvement of ITPKA in energy metabolism.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Inosito1-1,4,5-trisphosphat 3-kinase-a ; Actin ; Calcium ; Neurons ; Tumor Cells; Inositol 1,4,5-trisphosphate 3-kinase; Morphology; Expression; Itpka
ISSN (print) / ISBN 0304-3940
e-ISSN 0304-3940
Journal Neuroscience Letters
Quellenangaben Volume: 735, Issue: , Pages: , Article Number: 135206 Supplement: ,
Publisher Elsevier
Publishing Place Elsevier House, Brookvale Plaza, East Park Shannon, Co, Clare, 00000, Ireland
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Experimental Genetics (IEG)
Institute of Developmental Genetics (IDG)
Grants Else Kroner Fresenius Foundation
German Center for Diabetes Research
German Federal Ministry of Education and Research