TY - JOUR
T1 - Physiological relevance of the neuronal isoform of inositol-1,4,5-trisphosphate 3-kinases in mice
AU - Blechner, Christine
AU - Becker, Lore
AU - Fuchs, Helmut
AU - Rathkolb, Birgit
AU - Prehn, Cornelia
AU - Adler, Thure
AU - Calzada-Wack, Julia
AU - Garrett, Lillian
AU - Gailus-Durner, Valerie
AU - Morellini, Fabio
AU - Conrad, Susanne
AU - Hölter, Sabine M.
AU - Wolf, Eckhard
AU - Klopstock, Thomas
AU - Adamski, Jerzy
AU - Busch, Dirk
AU - de Angelis, Martin Hrabe
AU - Schmeisser, Michael J.
AU - Windhorst, Sabine
N1 - Publisher Copyright:
© 2020 Elsevier B.V.
PY - 2020/9/14
Y1 - 2020/9/14
N2 - 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.
AB - 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.
KW - Actin
KW - Calcium
KW - Inositol-1,4,5-trisphosphat 3-kinase-A
KW - Neurons
KW - Tumor cells
UR - http://www.scopus.com/inward/record.url?scp=85087118836&partnerID=8YFLogxK
U2 - 10.1016/j.neulet.2020.135206
DO - 10.1016/j.neulet.2020.135206
M3 - Article
C2 - 32593773
AN - SCOPUS:85087118836
SN - 0304-3940
VL - 735
JO - Neuroscience Letters
JF - Neuroscience Letters
M1 - 135206
ER -