Arf guanine nucleotide exchange factors (GEFs) can regulate cell adhesion, actin cytoskeletal dynamics, and membrane trafficking through the activation of the Arf small GTPases. We previously found that an Arf GTPase Activating Protein (GAP), CNT-2, was essential in controlling cell size and the cell death fate in the Q neuroblast lineage (Singhvi et al, 2011). We report here that several ArfGEFs control the asymmetric divisions of the Q cell daughters. Q.a and Q.p are both neuroblasts that divide to produce a larger neuronal precursor or neuron and a smaller cell fated to die. Loss of the cytohesin ArfGEF homolog GRP-1 resulted in the production of daughter cells that are more similar in size and in the transformation of the apoptotic daughter into its sister, resulting in the production of extra neurons. GRP-1's GEF activity, mediated by its SEC7 domain, is necessary for its role in the Q.p neuroblast. The loss of GRP-1, however, resulted in a phenotype that was less severe than the loss of CNT-2, suggesting that additional ArfGEFs remained to be identified. By screening for
grp-1 enhancers, we indeed identified two more ArfGEFs, EFA-6 and M02B7.5/Schizo/IQSEC, that are necessary for the Q.p division. Functional GFP-tagged GRP-1 proteins localized primarily to the nucleus, but targeting the GRP-1 SEC7 domain to different cellular compartments suggests that GRP-1 acts at the cell cortex. EFA-6 localized at the cell cortex, suggesting a functions there as well. Surprisingly, loss of GRP-1 and CNT-2 resulted in identical Q.a phenotypes, and neither
efa-6 nor M02B7.5 appears to function in this division. We will propose models that explain the differential involvement of these ArfGEFs in these two asymmetric divisions. Singhvi et al., Curr Biol. 2011 Jun 7;21(11):948-54.