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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
Molecular neurobiology | 2019

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.

Pubmed ID: 29802571

Research resources used in this publication

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Associated grants

  • Agency: Medical Research Council, United Kingdom
    Id: G0600759

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RRID:SCR_002368

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RRID:SCR_014294

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LSM Image Examiner (tool)

RRID:SCR_014344

Software used to compile images obtained from the Zeiss LSM 510 confocal microscope. The browser can be used for general image archiving and handling and interactive measurement in labs and workgroups. Features include orthogonal sectioning, 3D cut function, 3D view with calculation of single projections, and interactive measurement functions in the overlay dialog, such as scale bar, distance, and area.

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SH-SY5Y (tool)

RRID:CVCL_0019

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