Charles L. Saxe

The Regulation of Dictyostelium Development by Transmembrane Signalling

ABSTRACT. Dictyostelium discoideum has a well characterized life cycle where unicellular growth and multicellular development are separated events. Development is dependent upon signal transduction mediated by cell surface, cAMP receptor/G protein linkages. Secreted cAMP acts extracellularly as a primary signal and chemoattractant. There are 4 genes for the distinct cAMP receptor subtypes, CAR1, CAR2, CAR3 and CAR4. These subtypes are expressed with temporally and spatially specific patterns and cells carrying null mutations for each gene have distinct developmental phenotypes. These results indicate an essential role for cAMP signalling throughout Dictyostelium development to regulate such diverse pathways as cell motility, aggregation (multicellularity), cytodifferentiation, pattern formation and cell type‐specific gene expression.

Learning from the Slime Mold: Dictyostelium and Human Disease

When readers of this Journal think about Dictyostelium—rarely, if at all, I suspect—they may conjure up dim memories either of college laboratory demonstrations involving cell aggregation and cAMP or of watching the cells develop into tiny fruiting bodies made of spores and stalks. Yeasts and several invertebrate or vertebrate model systems are widely known for their contributions to our understanding of human disease, but Dictyostelium is seldom included in this list. Quietly, over the last few years, however, research on this social amoeba has revealed some common cellular characteristics shared across diverse phyla.

CHAPTER 177 – WASp/Scar/WAVE

The regulation of actin dynamics is central to variety of biological events, including cell motility, chemotaxis, nerve growth cone extension, and establishment of cell polarity. A number of signaling mechanisms control these events and play a role in determining the position and extent of new actin assembly. The understanding of the details is still incomplete, but many of these signals involve receptor stimulation and activation of members of the rho family of small GTPase. One mechanism by which signaling pathways regulate actin polymerization is by controlling the formation of new actin filaments. Activation of the Arp2/3 complex appears to be critical in the nucleation step of this process. In turn, activation of members of the Wiskott-Aldrich protein (WASp) family leads to activation of the Arp2/3 complex. WASp family members appear to play the role of signal integrator, responding to inputs from a variety of extracellular and intracellular signals and converting those signals into effects on actin dynamics.