RT Journal Article
SR Electronic
T1 Transmembrane Prolyl 4-Hydroxylase is a Novel Regulator of Calcium Signaling in Astrocytes
JF eneuro
JO eNeuro
FD Society for Neuroscience
SP ENEURO.0253-20.2020
DO 10.1523/ENEURO.0253-20.2020
VO 8
IS 1
A1 Nadiya Byts
A1 Subodh Sharma
A1 Jenny Laurila
A1 Prodeep Paudel
A1 Ilkka Miinalainen
A1 Veli-Pekka Ronkainen
A1 Reetta Hinttala
A1 Kid Törnquist
A1 Peppi Koivunen
A1 Johanna Myllyharju
YR 2021
UL http://www.eneuro.org/content/8/1/ENEURO.0253-20.2020.abstract
AB Prolyl 4-hydroxylases (P4Hs) have vital roles in regulating collagen synthesis and hypoxia response. A transmembrane P4H (P4H-TM) is a recently identified member of the family. Biallelic loss of function P4H-TM mutations cause a severe autosomal recessive intellectual disability syndrome in humans, but functions of P4H-TM are essentially unknown at cellular level. Our microarray data on P4h-tm−/− mouse cortexes where P4H-TM is abundantly expressed indicated expression changes in genes involved in calcium signaling and expression of several calcium sequestering ATPases was upregulated in P4h-tm−/− primary mouse astrocytes. Cytosolic and intraorganellar calcium imaging of P4h-tm−/− cells revealed that receptor-operated calcium entry (ROCE) and store-operated calcium entry (SOCE) and calcium re-uptake by mitochondria were compromised. HIF1, but not HIF2, was found to be a key mediator of the P4H-TM effect on calcium signaling. Furthermore, total internal reflection fluorescence (TIRF) imaging showed that calcium agonist-induced gliotransmission was attenuated in P4h-tm−/− astrocytes. This phenotype was accompanied by redistribution of mitochondria from distal processes to central parts of the cell body and decreased intracellular ATP content. Our data show that P4H-TM is a novel regulator of calcium dynamics and gliotransmission.