Differentiation-Induced Remodelling of Store-Operated Calcium Entry Is Independent of Neuronal or Glial Phenotype but Modulated by Cellular Context

Claire L. Whitworth, Christopher P.F. Redfern, Timothy R. Cheek (Lead / Corresponding author)

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)
140 Downloads (Pure)


Neurogenesis is a complex process leading to the generation of neuronal networks and glial cell types from stem cells or intermediate progenitors. Mapping subcellular and molecular changes accompanying the switch from proliferation to differentiation is vital for developing therapeutic targets for neurological diseases. Neuronal (N-type) and glial (S-type) phenotypes within the SH-SY5Y neuroblastoma cell line have distinct differentiation responses to 9-cis-retinoic acid (9cRA). In both cell phenotypes, these were accompanied at the single cell level by an uncoupling of Ca2+ store release from store-operated Ca2+ entry (SOCE), mediated by changes in the expression of calcium release-activated calcium pore proteins. This remodelling of calcium signalling was moderated by the predominant cell phenotype within the population. N- and S-type cells differed markedly in their phenotypic stability after withdrawal of the differentiation inducer, with the phenotypic stability of S-type cells, both morphologically and with respect to SOCE properties, in marked contrast to the lability of the N-type phenotype. Furthermore, the SOCE response of I-type cells, a presumed precursor to both N- and S-type cells, varied markedly in different cell environments. These results demonstrate the unique biology of neuronal and glial derivatives of common precursors and suggest that direct or indirect interactions between cell types are vital components of neurogenesis that need to be considered in experimental models.

Original languageEnglish
Pages (from-to)857-872
Number of pages16
JournalMolecular Neurobiology
Issue number2
Early online date26 May 2018
Publication statusPublished - 1 Feb 2019


  • Neurogenesis
  • Retinoic acid
  • Differentiation
  • calcium signalling
  • Orai1
  • STIM1
  • Neuronal
  • Glial
  • Nuroblastoma
  • Store-operated calcium entry

ASJC Scopus subject areas

  • Neuroscience (miscellaneous)
  • Neurology
  • Cellular and Molecular Neuroscience


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