Endocytosis Function of a Ligand-Gated Ion Channel Homolog in Caenorhabditis elegans

Patton, Andrea; Knuth, Sarah; Schaheen, Basil; Dang, Hope; Greenwald, Iva; Fares, Hanna

doi:10.1016/j.cub.2005.04.057

Cited by 53 publications

(65 citation statements)

References 26 publications

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“…Finally, we observed a decrease in expression of the coelomocyte marker cup-4::GFP (Patton et al, 2005), from an average of 3.7±0.2 cells (n=105) in wild type to 2.1±0.1 (n=53) in ceh-51(tm2123) ( descendants is compromised in mutants. Taken together, these results show that CEH-51 is required for the normal development of multiple MS tissue types.…”

Section: Loss Of Ceh-51 Function Results In Defects In Msderived Tissuesmentioning

confidence: 80%

The NK-2 class homeodomain factor CEH-51 and the T-box factor TBX-35 have overlapping function inC. elegansmesoderm development

et al. 2009

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The C. elegans MS blastomere, born at the 7-cell stage of embryogenesis, generates primarily mesodermal cell types, including pharynx cells, body muscles and coelomocytes. A presumptive null mutation in the T-box factor gene tbx-35, a target of the MED-1 and MED-2 divergent GATA factors, was previously found to result in a profound decrease in the production of MS-derived tissues, although the tbx-35(-) embryonic arrest phenotype was variable. We report here that the NK-2 class homeobox gene ceh-51 is a direct target of TBX-35 and at least one other factor, and that CEH-51 and TBX-35 share functions. Embryos homozygous for a ceh-51 null mutation arrest as larvae with pharynx and muscle defects, although these tissues appear to be specified correctly. Loss of tbx-35 and ceh-51 together results in a synergistic phenotype resembling loss of med-1 and med-2. Overexpression of ceh-51 causes embryonic arrest and generation of ectopic body muscle and coelomocytes. Our data show that TBX-35 and CEH-51 have overlapping function in MS lineage development. As T-box regulators and NK-2 homeodomain factors are both important for heart development in Drosophila and vertebrates, our results suggest that these regulators function in a similar manner in C. elegans to specify a major precursor of mesoderm.

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Section: Loss Of Ceh-51 Function Results In Defects In Msderived Tissuesmentioning

confidence: 80%

The NK-2 class homeodomain factor CEH-51 and the T-box factor TBX-35 have overlapping function inC. elegansmesoderm development

et al. 2009

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“…Whether pHCl-2 has an additional function in the nervous system remains unclear; microarray data suggest that it is not expressed in the head, brain and eyes of adult flies, or in the larval central nervous system (Chintapalli et al, 2007), but this broad survey would not necessarily detect expression in a small subset of neurons. Additionally, although we see pHCl-2 localized to the apical membrane of principal cells, we cannot rule out the possibility that it functions in apically enriched endosomal vesicles to regulate secretion, similar to CUP-4 in C. elegans, which is localized to endosomes and is necessary for endosomal trafficking, although its activating ligand, if any, is unknown (Patton, 2005). Nevertheless, whether it acts in endosomes or the apical membrane, our characterization of pHCl-2 illustrates the remarkable ability of the pLGICs to evolve diverse physiological functions.…”

Section: Discussionmentioning

confidence: 83%

The orphan pentameric ligand-gated ion channelpHCl-2is gated by pH and regulates fluid secretion inDrosophilaMalpighian tubules

Feingold

Starc

O’Donnell

et al. 2016

Journal of Experimental Biology

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Pentameric ligand-gated ion channels ( pLGICs) constitute a large protein superfamily in metazoa whose role as neurotransmitter receptors mediating rapid, ionotropic synaptic transmission has been extensively studied. Although the vast majority of pLGICs appear to be neurotransmitter receptors, the identification of pLGICs in non-neuronal tissues and homologous pLGIC-like proteins in prokaryotes points to biological functions, possibly ancestral, that are independent of neuronal signalling. Here, we report the molecular and physiological characterization of a highly divergent, orphan pLGIC subunit encoded by the pHCl-2 (CG11340) gene, in Drosophila melanogaster. We show that pHCl-2 forms a channel that is insensitive to a wide array of neurotransmitters, but is instead gated by changes in extracellular pH. pHCl-2 is expressed in the Malpighian tubules, which are non-innervated renal-type secretory tissues. We demonstrate that pHCl-2 is localized to the apical membrane of the epithelial principal cells of the tubules and that loss of pHCl-2 reduces urine production during diuresis. Our data implicate pHCl-2 as an important source of chloride conductance required for proper urine production, highlighting a novel role for pLGICs in epithelial tissues regulating fluid secretion and osmotic homeostasis.

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“…Basolateral endocytosis by the intestine was also be visualized using muscle-secreted GFP as a fluid-phase marker. In some cases a cup-4 mutation was also included in the assay to reduce uptake by coelomocytes and increase availability of the marker in the body cavity (Patton et al, 2005). RNAi was performed by the feeding method (Timmons and Fire, 1998).…”

Section: General Methods and Strainsmentioning

confidence: 99%

RAB-10 Is Required for Endocytic Recycling in theCaenorhabditis elegansIntestine

Chen

Schweinsberg

Vashist

et al. 2006

MBoC

186

385

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The endocytic pathway of eukaryotes is essential for the internalization and trafficking of macromolecules, fluid, membranes, and membrane proteins. One of the most enigmatic aspects of this process is endocytic recycling, the return of macromolecules (often receptors) and fluid from endosomes to the plasma membrane. We have previously shown that the EH-domain protein RME-1 is a critical regulator of endocytic recycling in worms and mammals. Here we identify the RAB-10 protein as a key regulator of endocytic recycling upstream of RME-1 in polarized epithelial cells of the Caenorhabditis elegans intestine. rab-10 null mutant intestinal cells accumulate abnormally abundant RAB-5-positive early endosomes, some of which are enlarged by more than 10-fold. Conversely most RME-1-positive recycling endosomes are lost in rab-10 mutants. The abnormal early endosomes in rab-10 mutants accumulate basolaterally recycling transmembrane cargo molecules and basolaterally recycling fluid, consistent with a block in basolateral transport. These results indicate a role for RAB-10 in basolateral recycling upstream of RME-1. We found that a functional GFP-RAB-10 reporter protein is localized to endosomes and Golgi in wild-type intestinal cells consistent with a direct role for RAB-10 in this transport pathway. INTRODUCTIONEndocytosis and endocytic trafficking controls the uptake and sorting of extracellular macromolecules as well as the components of the cell membrane itself, counterbalancing secretion and allowing a complex interplay between cells and their environment that is important for a myriad of cellular activities (Brodsky et al., 2001;Maxfield and McGraw, 2004). The steps involved in the uptake and trafficking of cargo within the endosomal system have been well described, but many of the components mediating these steps at the molecular level remain to be identified (Brodsky et al., 2001;Maxfield and McGraw, 2004). Many receptors and their associated ligands cluster into clathrincoated pits, whereas other types of cargo utilize clathrinindependent uptake mechanisms (Nichols, 2003;Gesbert et al., 2004). Plasma membrane invaginations pinch off into vesicles, uncoat, and then fuse with one another and with early endosomes. In early endosomes some ligand-receptor complexes dissociate because of the reduced pH of the endosomal lumen (Mukherjee et al., 1997). Many receptors then recycle to the plasma membrane (PM) either directly or indirectly via recycling endosomes (Mukherjee et al., 1997;Maxfield and McGraw, 2004). Many ligands do not recycle but instead are transported from early to late endosomes and eventually to lysosomes for degradation (Mukherjee et al., 1997). In polarized epithelial cells such as cultured Madin-Darby canine kidney (MDCK) cells, an additional layer of complexity in the endocytic pathway contributes to formation and/or maintenance of the specialized apical and basolateral domains (Nelson and Yeaman, 2001;Mostov et al., 2003;Hoekstra et al., 2004). Both the apical and basolateral membranes deliver cargo ...

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Endocytosis Function of a Ligand-Gated Ion Channel Homolog in Caenorhabditis elegans

Cited by 53 publications

References 26 publications

The NK-2 class homeodomain factor CEH-51 and the T-box factor TBX-35 have overlapping function inC. elegansmesoderm development

The NK-2 class homeodomain factor CEH-51 and the T-box factor TBX-35 have overlapping function inC. elegansmesoderm development

The orphan pentameric ligand-gated ion channelpHCl-2is gated by pH and regulates fluid secretion inDrosophilaMalpighian tubules

RAB-10 Is Required for Endocytic Recycling in theCaenorhabditis elegansIntestine

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