Extracellular polyphosphate signals through Ras and Akt to prime Dictyostelium discoideum cells for development.

Abstract:

:Linear chains of five to hundreds of phosphates called polyphosphate are found in organisms ranging from bacteria to humans, but their function is poorly understood. In Dictyostelium discoideum, polyphosphate is used as a secreted signal that inhibits cytokinesis in an autocrine negative feedback loop. To elucidate how cells respond to this unusual signal, we undertook a proteomic analysis of cells treated with physiological levels of polyphosphate and observed that polyphosphate causes cells to decrease levels of actin cytoskeleton proteins, possibly explaining how polyphosphate inhibits cytokinesis. Polyphosphate also causes proteasome protein levels to decrease, and in both Dictyostelium and human leukemia cells, decreases proteasome activity and cell proliferation. Polyphosphate also induces Dictyostelium cells to begin development by increasing expression of the cell-cell adhesion molecule CsA (also known as CsaA) and causing aggregation, and this effect, as well as the inhibition of proteasome activity, is mediated by Ras and Akt proteins. Surprisingly, Ras and Akt do not affect the ability of polyphosphate to inhibit proliferation, suggesting that a branching pathway mediates the effects of polyphosphate, with one branch affecting proliferation, and the other branch affecting development.

journal_name

J Cell Sci

journal_title

Journal of cell science

authors

Suess PM,Watson J,Chen W,Gomer RH

doi

10.1242/jcs.203372

subject

Has Abstract

pub_date

2017-07-15 00:00:00

pages

2394-2404

issue

14

eissn

0021-9533

issn

1477-9137

pii

jcs.203372

journal_volume

130

pub_type

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