RRC ID 45866
Author Teuliere J, Cordes S, Singhvi A, Talavera K, Garriga G.
Title Asymmetric neuroblast divisions producing apoptotic cells require the cytohesin GRP-1 in Caenorhabditis elegans.
Journal Genetics
Abstract Cytohesins are Arf guanine nucleotide exchange factors (GEFs) that regulate membrane trafficking and actin cytoskeletal dynamics. We report here that GRP-1, 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 GRP-1 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 GRP-1 functions with the previously described Arf GAP CNT-2 and two other Arf GEFs, EFA-6 and BRIS-1, to regulate the activity of Arf GTPases. In agreement with this model, we show that GRP-1's GEF activity, mediated by its SEC7 domain, is necessary for the posterior Q cell (Q.p) neuroblast division and that both GRP-1 and CNT-2 function in the Q.posterior Q daughter cell (Q.p) to promote its asymmetry. Although functional GFP-tagged GRP-1 proteins localized to the nucleus, the extra cell defects were rescued by targeting the Arf GEF activity of GRP-1 to the plasma membrane, suggesting that GRP-1 acts at the plasma membrane. The detection of endogenous GRP-1 protein at cytokinesis remnants, or midbodies, is consistent with GRP-1 functioning at the plasma membrane and perhaps at the cytokinetic furrow to promote the asymmetry of the divisions that require its function.
Volume 198(1)
Pages 229-47
Published 2014-9-1
DOI 10.1534/genetics.114.167189
PII genetics.114.167189
PMID 25053664
PMC PMC4174935
MeSH Active Transport, Cell Nucleus Animals Apoptosis* Asymmetric Cell Division* Caenorhabditis elegans / genetics* Caenorhabditis elegans / growth & development Caenorhabditis elegans / metabolism Caenorhabditis elegans Proteins / chemistry Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Cell Membrane / metabolism Cell Nucleus / metabolism Cytokinesis GTPase-Activating Proteins / genetics GTPase-Activating Proteins / metabolism Guanine Nucleotide Exchange Factors / chemistry Guanine Nucleotide Exchange Factors / genetics Guanine Nucleotide Exchange Factors / metabolism* Neural Stem Cells / metabolism* Neural Stem Cells / physiology Protein Binding Protein Structure, Tertiary
IF 4.015
Times Cited 8
C.elegans tm1956 tm1877 tm3124 tm1447