Insights Into Aggregation‐Delayed Phenotype of Dictyostelium discoideum

Dictyostelium discoideum is a cellular model that has been widely used in cell signal research focusing on different cellular and developmental processes. The unique lifecycle of these cells-which involves switching between vegetative and development phases-makes Dictyostelium a reliable model for investigations in this field. The ability to switch between these phases depends mainly on the availability of nutrients. Specifically, the vegetative phase of Dictyostelium cells is initiated when food is plentiful. This phase is characterized by the unicellular form of this organism, in which it is able to hunt for bacteria and actively divide by mitosis. However, when nutrients are depleted, certain cellular signals are activated that stimulate the development phase, which commences with cell chemotaxis toward cyclic AMP to form aggregates. Based on previously collected data, aggregation-regulating signals in Dictyostelium are thoroughly explained herein. Heterotrimeric G protein signals and downstream effectors are thought to be included in this paradigm, as blocking these signals leads to the aggregation-minus phenotype. Recently, Dictyostelium was used to detect the effect of natural products, some of which caused a noticeable delay of the aggregation stage. However, no clear evidence has been obtained that explains why aggregation is delayed or the science behind this phenomenon. This review provides insights into regulatory factors, beyond the key aggregation regulators, that possibly contribute to the aggregation-delayed phenotype of Dictyostelium cells. The discussion in this review will enhance understanding of the importance of divalent cations/ions in this phenotype.