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Differentiation-induced remodelling of store-operated calcium entry is independent of neuronal or glial phenotype but modulated by cellular context

Lookup NU author(s): Claire Whitworth, Dr Chris RedfernORCiD, Dr Tim Cheek



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


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.

Publication metadata

Author(s): Whitworth CL, Redfern CPF, Cheek TR

Publication type: Article

Publication status: Published

Journal: Molecular Neurobiology

Year: 2019

Volume: 56

Issue: 2

Pages: 857-872

Print publication date: 01/02/2019

Online publication date: 26/05/2018

Acceptance date: 09/05/2018

Date deposited: 30/05/2018

ISSN (print): 0893-7648

ISSN (electronic): 1559-1182

Publisher: Springer


DOI: 10.1007/s12035-018-1112-y

PubMed id: 29802571


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