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Transmembrane Prolyl 4-Hydroxylase is a Novel Regulator of Calcium Signaling in Astrocytes.
Byts, Nadiya; Sharma, Subodh; Laurila, Jenny; Paudel, Prodeep; Miinalainen, Ilkka; Ronkainen, Veli-Pekka; Hinttala, Reetta; Törnquist, Kid; Koivunen, Peppi; Myllyharju, Johanna.
Afiliación
  • Byts N; Oulu Center for Cell-Matrix Research, Biocenter Oulu and Faculty of Biochemistry and Molecular Medicine, University of Oulu, Oulu 90014, Finland.
  • Sharma S; Oulu Center for Cell-Matrix Research, Biocenter Oulu and Faculty of Biochemistry and Molecular Medicine, University of Oulu, Oulu 90014, Finland.
  • Laurila J; Oulu Center for Cell-Matrix Research, Biocenter Oulu and Faculty of Biochemistry and Molecular Medicine, University of Oulu, Oulu 90014, Finland.
  • Paudel P; Oulu Center for Cell-Matrix Research, Biocenter Oulu and Faculty of Biochemistry and Molecular Medicine, University of Oulu, Oulu 90014, Finland.
  • Miinalainen I; Biocenter Oulu, University of Oulu, Oulu 90014, Finland.
  • Ronkainen VP; Biocenter Oulu, University of Oulu, Oulu 90014, Finland.
  • Hinttala R; Biocenter Oulu, University of Oulu, Oulu 90014, Finland.
  • Törnquist K; PEDEGO Research Unit, Faculty of Medicine, University of Oulu, Oulu 90014, Finland.
  • Koivunen P; Cell Biology, Faculty of Science and Engineering, Åbo Akademi University, Turku 20500, Finland.
  • Myllyharju J; Minerva Foundation Institute for Medical Research, Biomedicum Helsinki, Helsinki 00290, Finland.
eNeuro ; 8(1)2021.
Article en En | MEDLINE | ID: mdl-33298456
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Astrocitos / Señalización del Calcio Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: ENeuro Año: 2021 Tipo del documento: Article País de afiliación: Finlandia Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Astrocitos / Señalización del Calcio Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: ENeuro Año: 2021 Tipo del documento: Article País de afiliación: Finlandia Pais de publicación: Estados Unidos