PUBLICATION

Calcium sparks enhance the tissue fluidity within epithelial layers and promote apical extrusion of transformed cells

Authors
Kuromiya, K., Aoki, K., Ishibashi, K., Yotabun, M., Sekai, M., Tanimura, N., Iijima, S., Ishikawa, S., Kamasaki, T., Akieda, Y., Ishitani, T., Hayashi, T., Toda, S., Yokoyama, K., Lee, C.G., Usami, I., Inoue, H., Takigawa, I., Gauquelin, E., Sugimura, K., Hino, N., Fujita, Y.
ID
ZDB-PUB-220714-10
Date
2022
Source
Cell Reports   40: 111078 (Journal)
Registered Authors
Akieda, Yuki
Keywords
AHNAK2, CP: Cell biology, CP: Developmental biology, Cdc42, RasV12, TRPC1, apical extrusion, calcium sparks, cell competition, epithelia, phospho-SILAC screening, zebrafish larvae
MeSH Terms
  • Animals
  • Calcium/metabolism
  • Calcium Signaling*
  • Cell Movement
  • Dogs
  • Epithelial Cells/metabolism
  • Madin Darby Canine Kidney Cells
  • Zebrafish*/metabolism
PubMed
35830802 Full text @ Cell Rep.
Abstract
In vertebrates, newly emerging transformed cells are often apically extruded from epithelial layers through cell competition with surrounding normal epithelial cells. However, the underlying molecular mechanism remains elusive. Here, using phospho-SILAC screening, we show that phosphorylation of AHNAK2 is elevated in normal cells neighboring RasV12 cells soon after the induction of RasV12 expression, which is mediated by calcium-dependent protein kinase C. In addition, transient upsurges of intracellular calcium, which we call calcium sparks, frequently occur in normal cells neighboring RasV12 cells, which are mediated by mechanosensitive calcium channel TRPC1 upon membrane stretching. Calcium sparks then enhance cell movements of both normal and RasV12 cells through phosphorylation of AHNAK2 and promote apical extrusion. Moreover, comparable calcium sparks positively regulate apical extrusion of RasV12-transformed cells in zebrafish larvae as well. Hence, calcium sparks play a crucial role in the elimination of transformed cells at the early phase of cell competition.
Genes / Markers
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Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
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Mapping