The contractile vacuole is part of the polarity circuit of the cell, with redistribution to the rear and exocytosis contributing to signal relay and cellular streaming

Abstract

Collective cell migration is a fascinating process where a group of cells moves in a coordinated manner contributing to biological processes like morphogenesis, wound healing and pathological conditions like cancer metastasis. The social amoeba Dictyostelium discoideum is a model organism for studying collective cell migration as cells align in a head-to-tail manner to form streams and later differentiate and migrate as sheets during fruiting body formation. The majority of communication is achieved by secreting cAMP and by migrating towards this extracellular signal. This work has shown that the contractile vacuole (CV), the organelle responsible for osmoregulation, localizes at the rear of polarized D. discoideum cells. This redistribution is critical for recruiting cells into streams and cAMP secretion/relay and has been shown to be regulated by CV exocytosis. Additionally, these studies revealed that the cAMP transporter AbcC8, the transporter identified for cAMP signal relay during aggregation, localizes to the CV network. Two mutant cell lines, htt- and LvsA-, both of which have major CV defects, generated weak cAMP waves and did not stream, providing evidence for the role of the CV in this process. CV discharge is regulated by an exocytic event, that has been described as kiss-and-run. During this process, the CV fuses with the plasma membrane (PM) and the contents are released. Phosphatidylinositol (4,5)-bisphosphate [PI(4,5)P2], which is the main anionic phosphoinositide of the PM, has been strongly implicated in CV exocytic events. This work shows that the rear CV localization is part of the cell polarity network and is critical for streaming during early aggregation. PI(4,5)P2 appears to be a key player in regulating CV function. Elucidating the molecular mechanisms of CV exocytosis and polarized redistribution is crucial to improve our understanding of a wide range of physiological and pathological processes like morphogenesis and tumor invasion.