Asymmetric Neuroblast Divisions Producing Apoptotic Cells Require the Cytohesin GRP-1 in Caenorhabditis elegans

摘要

Cytohesins are Arf guanine nucleotide exchange factors (GEFs) that regulate membrane trafficking and actin cytoskeletal dynamics. We report here that , the sole Caenorhabditis elegans cytohesin, controls the asymmetric divisions of certain neuroblasts that divide to produce a larger neuronal precursor or neuron and a smaller cell fated to die. In the Q neuroblast lineage, loss of led to the production of daughter cells that are more similar in size and to the transformation of the normally apoptotic daughter into its sister, resulting in the production of extra neurons. Genetic interactions suggest that functions with the previously described Arf GAP and two other Arf GEFs, and , to regulate the activity of Arf GTPases. In agreement with this model, we show that ’s GEF activity, mediated by its SEC7 domain, is necessary for the posterior Q cell (Q.p) neuroblast division and that both and function in the Q.posterior Q daughter cell (Q.p) to promote its asymmetry. Although functional GFP-tagged proteins localized to the nucleus, the extra cell defects were rescued by targeting the Arf GEF activity of to the plasma membrane, suggesting that acts at the plasma membrane. The detection of endogenous protein at cytokinesis remnants, or midbodies, is consistent with functioning at the plasma membrane and perhaps at the cytokinetic furrow to promote the asymmetry of the divisions that require its function.