| First Author | Byts N | Year | 2021 |
| Journal | eNeuro | Volume | 8 |
| Issue | 1 | PubMed ID | 33298456 |
| Mgi Jnum | J:313923 | Mgi Id | MGI:6803503 |
| Doi | 10.1523/ENEURO.0253-20.2020 | Citation | Byts N, et al. (2021) Transmembrane Prolyl 4-Hydroxylase is a Novel Regulator of Calcium Signaling in Astrocytes. eNeuro 8(1):ENEURO.0253-20.2020 |
| abstractText | 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. |
