RRC ID 75848
Author 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 CG, Usami I, Inoue H, Takigawa I, Gauquelin E, Sugimura K, Hino N, Fujita Y.
Title Calcium sparks enhance the tissue fluidity within epithelial layers and promote apical extrusion of transformed cells.
Journal 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.
Volume 40(2)
Pages 111078
Published 2022-7-12
DOI 10.1016/j.celrep.2022.111078
PII S2211-1247(22)00876-2
PMID 35830802
MeSH Animals Calcium / metabolism Calcium Signaling* Cell Movement Dogs Epithelial Cells / metabolism Madin Darby Canine Kidney Cells Zebrafish* / metabolism
IF 8.109
Zebrafish Krt4p:Gal4 UAS:GFP