TRPC1- and TRPC3-dependent Ca, javax.xml.bind.JAXBElement@c75b5d8, signaling in mouse cortical astrocytes affects injury-evoked astrogliosis in vivo.

TRPC1- and TRPC3-dependent Ca, javax.xml.bind.JAXBElement@c75b5d8, signaling in mouse cortical astrocytes affects injury-evoked astrogliosis in vivo. Belkacemi, T., Niermann, A., Hofmann, L., Wissenbach, U., Birnbaumer, L., Leidinger, P., Backes, C., Meese, E., Keller, A., Bai, X., Scheller, A., Kirchhoff, F., Philipp, S. E, Weissgerber, P., Flockerzi, V., & Beck, A. Glia, 65:1535–1549, September, 2017.
doi abstract bibtex

Following brain injury astrocytes change into a reactive state, proliferate and grow into the site of lesion, a process called astrogliosis, initiated and regulated by changes in cytoplasmic Ca . Transient receptor potential canonical (TRPC) channels may contribute to Ca influx but their presence and possible function in astrocytes is not known. By RT-PCR and RNA sequencing we identified transcripts of Trpc1, Trpc2, Trpc3, and Trpc4 in FACS-sorted glutamate aspartate transporter (GLAST)-positive cultured mouse cortical astrocytes and subcloned full-length Trpc1 and Trpc3 cDNAs from these cells. Ca entry in cortical astrocytes depended on TRPC3 and was increased in the absence of Trpc1. After co-expression of Trpc1 and Trpc3 in HEK-293 cells both proteins co-immunoprecipitate and form functional heteromeric channels, with TRPC1 reducing TRPC3 activity. In vitro, lack of Trpc3 reduced astrocyte proliferation and migration whereas the TRPC3 gain-of-function moonwalker mutation and Trpc1 deficiency increased astrocyte migration. In vivo, astrogliosis and cortex edema following stab wound injury were reduced in Trpc3 but increased in Trpc1 mice. In summary, our results show a decisive contribution of TRPC3 to astrocyte Ca signaling, which is even augmented in the absence of Trpc1, in particular following brain injury. Targeted therapies to reduce TRPC3 channel activity in astrocytes might therefore be beneficial in traumatic brain injury.

@Article{Belkacemi2017,
  author          = {Belkacemi, Thabet and Niermann, Alexander and Hofmann, Laura and Wissenbach, Ulrich and Birnbaumer, Lutz and Leidinger, Petra and Backes, Christina and Meese, Eckart and Keller, Andreas and Bai, Xianshu and Scheller, Anja and Kirchhoff, Frank and Philipp, Stephan E and Weissgerber, Petra and Flockerzi, Veit and Beck, Andreas},
  title           = {TRPC1- and TRPC3-dependent Ca, javax.xml.bind.JAXBElement@c75b5d8, signaling in mouse cortical astrocytes affects injury-evoked astrogliosis in vivo.},
  journal         = {Glia},
  year            = {2017},
  volume          = {65},
  pages           = {1535--1549},
  month           = sep,
  issn            = {1098-1136},
  abstract        = {Following brain injury astrocytes change into a reactive state, proliferate and grow into the site of lesion, a process called astrogliosis, initiated and regulated by changes in cytoplasmic Ca  . Transient receptor potential canonical (TRPC) channels may contribute to Ca  influx but their presence and possible function in astrocytes is not known. By RT-PCR and RNA sequencing we identified transcripts of Trpc1, Trpc2, Trpc3, and Trpc4 in FACS-sorted glutamate aspartate transporter (GLAST)-positive cultured mouse cortical astrocytes and subcloned full-length Trpc1 and Trpc3 cDNAs from these cells. Ca  entry in cortical astrocytes depended on TRPC3 and was increased in the absence of Trpc1. After co-expression of Trpc1 and Trpc3 in HEK-293 cells both proteins co-immunoprecipitate and form functional heteromeric channels, with TRPC1 reducing TRPC3 activity. In vitro, lack of Trpc3 reduced astrocyte proliferation and migration whereas the TRPC3 gain-of-function moonwalker mutation and Trpc1 deficiency increased astrocyte migration. In vivo, astrogliosis and cortex edema following stab wound injury were reduced in Trpc3  but increased in Trpc1  mice. In summary, our results show a decisive contribution of TRPC3 to astrocyte Ca  signaling, which is even augmented in the absence of Trpc1, in particular following brain injury. Targeted therapies to reduce TRPC3 channel activity in astrocytes might therefore be beneficial in traumatic brain injury.},
  chemicals       = {TRPC Cation Channels, TRPC3 cation channel, Trpc5 protein, mouse, Trpc6 protein, mouse, transient receptor potential cation channel, subfamily C, member 1},
  citation-subset = {IM},
  completed       = {2018-04-12},
  country         = {United States},
  doi             = {10.1002/glia.23180},
  issn-linking    = {0894-1491},
  issue           = {9},
  keywords        = {Animals; Astrocytes, metabolism, pathology; Brain Edema, etiology, metabolism, pathology; Calcium Signaling, physiology; Cell Movement, physiology; Cell Proliferation, physiology; Cerebral Cortex, injuries, metabolism, pathology; Disease Models, Animal; Gliosis, etiology, metabolism, pathology; HEK293 Cells; Humans; Male; Mice, 129 Strain; Mice, Inbred C57BL; Mice, Knockout; TRPC Cation Channels, genetics, metabolism; Wounds, Stab, metabolism, pathology; glia; ion channels; membrane currents; migration; proliferation; stab wound injury},
  mid             = {NIHMS881833},
  nlm-id          = {8806785},
  owner           = {NLM},
  pmc             = {PMC5526095},
  pmid            = {28636132},
  pubmodel        = {Print-Electronic},
  pubstatus       = {ppublish},
  revised         = {2018-05-17},
}

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