Transmembrane Prolyl 4-Hydroxylase is a Novel Regulator of Calcium Signaling in Astrocytes

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http://hdl.handle.net/10138/327783

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Byts , N , Sharma , S , Laurila , J , Paudel , P , Miinalainen , I , Ronkainen , V-P , Hinttala , R , Törnquist , K , Koivunen , P & Myllyharju , J 2021 , ' Transmembrane Prolyl 4-Hydroxylase is a Novel Regulator of Calcium Signaling in Astrocytes ' , eNeuro , vol. 8 , no. 1 , ARTN 0253-20.2020 . https://doi.org/10.1523/ENEURO.0253-20.2020

Title: Transmembrane Prolyl 4-Hydroxylase is a Novel Regulator of Calcium Signaling in Astrocytes
Author: Byts, Nadiya; Sharma, Subodh; Laurila, Jenny; Paudel, Prodeep; Miinalainen, Ilkka; Ronkainen, Veli-Pekka; Hinttala, Reetta; Törnquist, Kid; Koivunen, Peppi; Myllyharju, Johanna
Contributor organization: Medicum
Date: 2021
Language: eng
Number of pages: 23
Belongs to series: eNeuro
ISSN: 2373-2822
DOI: https://doi.org/10.1523/ENEURO.0253-20.2020
URI: http://hdl.handle.net/10138/327783
Abstract: Prolyl 4-hydroxylases (P4Hs) have vital roles in regulating collagen synthesis and hypoxia response. A trans membrane 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.
Subject: calcium signaling
hypoxia-inducible factor
prolyl 4-hydroxylase
vesicular exocytosis
ENDOPLASMIC-RETICULUM STRESS
MITOCHONDRIAL CA2+ UPTAKE
INTRACELLULAR CALCIUM
CA2+-DEPENDENT EXOCYTOSIS
SUPEROXIDE-DISMUTASE
PREFRONTAL CORTEX
PROTEIN-SYNTHESIS
OXIDATIVE STRESS
GENE-EXPRESSION
DOWN-REGULATION
3112 Neurosciences
3124 Neurology and psychiatry
Peer reviewed: Yes
Rights: cc_by
Usage restriction: openAccess
Self-archived version: publishedVersion


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