was created by the Gene Knockout Project at the Oklahoma Medical Research Foundation and was obtained from the C

was created by the Gene Knockout Project at the Oklahoma Medical Research Foundation and was obtained from the C. apoptotic fate in the smaller Q.p AS-252424 daughter but did not affect the size asymmetry of the Q.p daughters. This function of TOE-2 required the DEP domain but not localization to the membrane. We propose that TOE-2 ensures an apoptotic fate for the small Q.a daughter by promoting asymmetry in the daughter cell sizes of the Q.a neuroblast division but by a mechanism that is independent of cell size in the Q.p division. caspases, only plays a major role in apoptosis (Denning et al., 2013). In mammals, multiple caspases regulate apoptosis (Shaham, 1998; Elmore, 2007). In certain contexts, these mammalian caspases can be activated in response to external signals (Ashkenazi and Dixit, 1998); by contrast, we know less about how the apoptotic fate is Rabbit Polyclonal to Collagen XIV alpha1 specified in (Potts and Cameron, 2011). Both caspase-dependent and caspase-independent pathways regulate apoptosis, and genetic studies suggest that PIG-1, a member of the AMP-activated protein kinase family, acts in parallel to CED-3 (Cordes et al., 2006). The demonstration that a homolog of the Sp1 transcription factor regulates both and transcription in specific cells that are fated to die supports the hypothesis that PIG-1 and AS-252424 CED-3 act in parallel (Hirose and Horvitz, 2013). Divisions that generate apoptotic cells are asymmetric, producing a larger cell that survives and a smaller cell that dies. Loss of PIG-1 leads to daughter cells that are more symmetric in size, suggesting that cell size contributes to the apopototic fate (Cordes et al., 2006; Ou et al., 2010). In the Q lineage, both the anterior (Q.a) and posterior AS-252424 (Q.p) daughter cells divide to generate a smaller apoptotic cell, but the two divisions employ distinct mechanisms to generate this asymmetry: a spindle-dependent mechanism generates Q.p asymmetry, and a spindle-independent mechanism generates Q.a asymmetry (Ou et al., 2010). Here, we describe a role for TOE-2 in the regulation of the apoptotic fate. TOE-2 is a poorly understood DEP (domain found in Dishevelled, EGL-10 and Pleckstrin) domain-containing protein that is a target of the worm ERK ortholog MPK-1, a negative regulator of germline apoptosis (Arur et al., 2009). DEP domains can promote localization to the plasma membrane (Axelrod et al., 1998; Wong et al., 2000), and this localization allows DEP domain-containing proteins to regulate signals that are sent from cell surface receptors to downstream effectors. For example, regulator of G-protein signaling proteins (RGSs) regulate AS-252424 heterotrimeric GTPases, which are involved in transducing signals from various extracellular factors (Neves et al., 2002). RGSs are AS-252424 GTPase activating proteins (GAPs) that modulate G-protein signaling by enhancing the hydrolytic activity of G, thus reducing the amount of time that the G-protein subunits are dissociated from one another C the time when G is active (Chen and Hamm, 2006). In addition to their interaction with G proteins, RGSs also probably bind, through their DEP domains, to G-protein-coupled receptors (GPCRs). The yeast RGS Sst2 binds to the C-terminal tail of the GPCR Ste2, leading to an attenuation of trimeric G-protein activity (Ballon et al., 2006). We provide evidence that TOE-2 functions differently in the Q.a and Q.p divisions. Although DEP domains are thought to facilitate membrane localization, we find that the DEP domain is not required for the cortical localization of TOE-2 but is required for its function in promoting apoptosis in the Q.p division. In contrast with the.