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

• Published in: Journal of cell science Vol. 130; no. 14; pp. 2394 - 2404
• Main Authors: Suess, Patrick M, Watson, Jacob, Chen, Wensheng, Gomer, Richard H
• Format: Journal Article
• Language: English
• Published: England The Company of Biologists Ltd 15.07.2017
• Subjects: Actin; AKT protein; Autocrine signalling; Bacteria; Cell adhesion; Cell adhesion & migration; Cell adhesion molecules; Cell proliferation; Cytokinesis; Cytoskeleton; Dictyostelium - cytology; Dictyostelium - metabolism; Eukaryotes; Feedback loops; Humans; Leukemia; Negative feedback; Phosphates; Polyphosphates - metabolism; Proteasomes; Proteins; Proteomics; Proto-Oncogene Proteins c-akt - metabolism; Ras protein; ras Proteins - metabolism; Signal Transduction; Development; Dictyostelium; Polyphosphate; Akt; Ras; Proteasome
• ISSN: 0021-9533; 1477-9137
• DOI: 10.1242/jcs.203372

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 , 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 and human leukemia cells, decreases proteasome activity and cell proliferation. Polyphosphate also induces 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.