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Cell Calcium. 2013 Dec;54(6):404-15. doi: 10.1016/j.ceca.2013.09.003. Epub 2013 Oct 16.

TRPM7 triggers Ca2+ sparks and invadosome formation in neuroblastoma cells.

Author information

1
Division of Cell Biology I, The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands.

Abstract

Cell migration depends on the dynamic formation and turnover of cell adhesions and is tightly controlled by actomyosin contractility and local Ca2+ signals. The divalent cation channel TRPM7 (Transient Receptor Potential cation channel, subfamily Melastatin, member 7) has recently received much attention as a regulator of cell adhesion, migration and (localized) Ca2+ signaling. Overexpression and knockdown of TRPM7 affects actomyosin contractility and the formation of cell adhesions such as invadosomes and focal adhesions, but the role of TRPM7-mediated Ca2+ signals herein is currently not understood. Using Total Internal Reflection Fluorescence (TIRF) Ca2+ fluorometry and a novel automated analysis routine we have addressed the role of Ca2+ in the control of invadosome dynamics in N1E-115 mouse neuroblastoma cells. We find that TRPM7 promotes the formation of highly repetitive and localized Ca2+ microdomains or "Ca2+ sparking hotspots" at the ventral plasma membrane. Ca2+ sparking appears strictly dependent on extracellular Ca2+ and is abolished by TRPM7 channel inhibitors such as waixenicin-A. TRPM7 inhibition also induces invadosome dissolution. However, invadosome formation is (functionally and spatially) dissociated from TRPM7-mediated Ca2+ sparks. Rather, our data indicate that TRPM7 affects actomyosin contractility and invadosome formation independent of Ca2+ influx.

KEYWORDS:

2-APB; 2-aminoethyl diphenylborinate; Adhesion; BK; Ca(2+) imaging; Ca(2+) signaling; ECM; FA; FC; Invadosome; TIRF; TIRF microscopy; TRPM7; Total Internal Reflection Fluorescence (microscopy); Transient Receptor Potential cation channel, subfamily Melastatin, member 7; bradykinin; extracellular matrix; focal adhesion; focal complex

PMID:
24176224
PMCID:
PMC4912378
DOI:
10.1016/j.ceca.2013.09.003
[Indexed for MEDLINE]
Free PMC Article

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