Regulation of Rap1 activity is required for differential adhesion, cell-type patterning and morphogenesis inDictyostelium

Abstract

cells do not exhibit impaired motility or chemotaxis, indicating that RapGAPB might only regulate specific roles of Rap1. Importantly, we also found that RapGAPB regulates Rap1 activity during multicellular development and is required for normal morphogenesis. First, streams of aggregating rapGAPB -cells break up as a result of decreased cell-cell adhesion. Second, rapGAPB -cells exhibit cell-autonomous defects in prestalk cell patterning. Using cell-type-specific markers, we demonstrate that RapGAPB is required for the correct sorting behaviour of different cell types. Finally, we show that inactivation of RapGAPB affects prestalk and prespore cell adhesion. We therefore propose that a possible mechanism for RapGAPBregulated cell sorting is through differential adhesion. Supplementary material available online at

RAP1-mediated MEK/ERK pathway defects in Kabuki syndrome

“…RAP1A, and the highly related protein RAP1B (95% amino acid identity), belong to the Ras family of small GTPases, regulating various cellular processes such as cell adhesion and migration (14)(15)(16); studies in Xenopus and zebrafish have shown that rap1a and rap1b morphants exhibit similar gastrulation defects, highlighting the important role of both proteins in early development (17). RAP1 is known to exert opposing effects on the MAPK pathway (18), depending on tissue-and cell-specific context: an activating effect through BRAF (19,20) and a repressive effect through RAF1 (21).…”

Gene discovery by chemical mutagenesis and whole-genome sequencing in Dictyostelium

“…These results suggest that our So far, we have relied on multiple alleles and on published results to validate our screen results. The highest numbers of alleles were found in rapgapB and tgrB1, and we know that TgrB1 and TgrC1 interact to regulate development (Hirose et al 2015) and that rapgapB encodes a RapA GTPase regulatory protein B that regulates cell-cell and cell-substrate adhesion (Parkinson et al 2009). This knowledge and the availability of molecular tools allowed us to perform direct causality tests of these mutations.…”

Redundant and unique roles of coronin proteins in Dictyostelium

“…For example, myosin heavy chain deficient D. discoideum cells do not form fruiting bodies but stop already at the mound stage, an early stage of development. Mutants in which the activation of the small GTPase Rap which regulates actin assembly at the posterior pole during chemotaxis, is altered have a cell adhesion defect during aggregation and a cell patterning defect in the post aggregation stage [34,40].…”