Harmar AJ (2001) Genome Biol "Family-B G-protein-coupled receptors."

Harmar AJ

[Genome Biol, 2001]

SUMMARY: All G-protein-coupled receptors (GPCRs) share a common molecular architecture (with seven putative transmembrane segments) and a common signaling mechanism, in that they interact with G proteins (heterotrimeric GTPases) to regulate the synthesis of intracellular second messengers such as cyclic AMP, inositol phosphates, diacylglycerol and calcium ions. Historically, GPCRs have been classified into six families, which were thought to be unrelated; three of these are found in vertebrates. Recent work has identified several new GCPR families and suggested the possibility of a common evolutionary origin for all of them. Family B (the secretin-receptor family or ''family 2'') of the GPCRs is a small but structurally and functionally diverse group of proteins that includes receptors for polypeptide hormones, molecules thought to mediate intercellular interactions at the plasma membrane and a group of Drosophila proteins that regulate stress responses and longevity. Family-B GPCRs have been found in all animal species investigated, including mammals, Caenorhabditis elegans and Drosophila melanogaster, but not in plants, fungi or prokaryotes. In this article, I describe the structures and functions of family-B GPCRs and propose a simplified nomenclature for these proteins.

NK887

Caenorhabditis elegans

Armenti ST et al. (2012) Subcell Biochem "Adherens junctions in C. elegans embryonic morphogenesis."

Nance J, Armenti ST

[Subcell Biochem, 2012]

Caenorhabditis elegans provides a simplified, in vivo model system in which to study adherens junctions (AJs) and their role in morphogenesis. The core AJ components-HMR-1/E-cadherin, HMP-2/-catenin and HMP-1/-catenin-were initially identified through genetic screens for mutants with body axis elongation defects. In early embryos, AJ proteins are found at sites of contact between blastomeres, and in epithelial cells AJ proteins localize to the multifaceted apical junction (CeAJ)-a single structure that combines the adhesive and barrier functions of vertebrate adherens and tight junctions. The apically localized polarity proteins PAR-3 and PAR-6 mediate formation and maturation of junctions, while the basolaterally localized regulator LET-413/Scribble ensures that junctions remain apically positioned. AJs promote robust adhesion between epithelial cells and provide mechanical resistance for the physical strains of morphogenesis. However, in contrast to vertebrates, C. elegans AJ proteins are not essential for general cell adhesion or for epithelial cell polarization. A combination of conserved and novel proteins localizes to the CeAJ and works together with AJ proteins to mediate adhesion.

Zilberman Y et al. (2017) J Cell Biol "Cdc42 regulates junctional actin but not cell polarization in the Caenorhabditis elegans epidermis."

Abrams J, Zilberman Y, Nance J, Anderson DC

[J Cell Biol, 2017]

During morphogenesis, adherens junctions (AJs) remodel to allow changes in cell shape and position while preserving adhesion. Here, we examine the function of Rho guanosine triphosphatase CDC-42 in AJ formation and regulation during Caenorhabditis elegans embryo elongation, a process driven by asymmetric epidermal cell shape changes. cdc-42 mutant embryos arrest during elongation with epidermal ruptures. Unexpectedly, we find using time-lapse fluorescence imaging that cdc-42 is not required for epidermal cell polarization or junction assembly, but rather is needed for proper junctional actin regulation during elongation. We show that the RhoGAP PAC-1/ARHGAP21 inhibits CDC-42 activity at AJs, and loss of PAC-1 or the interacting linker protein PICC-1/CCDC85A-C blocks elongation in embryos with compromised AJ function. pac-1 embryos exhibit dynamic accumulations of junctional F-actin and an increase in AJ protein levels. Our findings identify a previously unrecognized molecular mechanism for inhibiting junctional CDC-42 to control actin organization and AJ protein levels during epithelial morphogenesis.

Picture from Nehrke K et al. (2002) J Biol Chem "The NHX family of Na+-H+ exchangers in Caenorhabditis elegans."

Q and R, the nhx-9 promoter drove GFP expression in the excretory cell (ec) as well as in the phasmid sensory organs in the tail (phm) and the posterior intestine (int; AI and AJ).

Picture from Hsu TY et al. (2010) Curr Biol "Engulfment of apoptotic cells in C. elegans is mediated by integrin alpha/SRC ...."

(Aa-Aj) INA-1::GFP is enriched in the pseudopods extending around apoptotic cells. Time-lapse images of INA-1::GFP (Aa-Ae) and differential interference contrast (DIC; Af-Aj) during cell corpse internalization in an embryo expressing Pced-1ina-1::gfp are shown. 0 min indicates the time point at which INA-1::GFP was first seen to accumulate at the contact site with C3. Arrowheads indicate the apoptotic cell (C3); arrows indicate the engulfing cell (ABplaapppp). Scale bar in (Aa) represents 5 um.

AX2157

Caenorhabditis elegans

AX2178

Caenorhabditis elegans

Tsur A et al. (2015) Dev Cell "ULP-2 SUMO Protease Regulates E-Cadherin Recruitment to Adherens Junctions."

Tsur A, Bening Abu-Shach U, Broday L

[Dev Cell, 2015]

Adherens junctions (AJs) are membrane-anchored structures composed of E-cadherin and associated proteins, including catenins and actin. The unique plasticity of AJs mediates both the rigidity and flexibility of cell-cell contacts essential for embryonic morphogenesis and adult tissue remodeling. We identified the SUMO protease ULP-2 as a regulator of AJ assembly and show that dysregulated ULP-2 activity impairs epidermal morphogenesis in Caenorhabditis elegans embryos. The conserved cytoplasmic tail of HMR-1/E-cadherin is sumoylated and is a target of ULP-2 desumoylation activity. Coupled sumoylation and desumoylation of HMR-1 are required for its recruitment to the subapical membrane during AJ assembly and the formation of the linkages between AJs and the apical actin cytoskeleton. Sumoylation weakens HMR-1 binding to HMP-2/-catenin. Our study provides a mechanistic link between the dynamic nature of the SUMO machinery and AJ plasticity and highlight sumoylation as a molecular switch that modulates the binding of E-cadherin to the actin cytoskeleton.

NK885

Caenorhabditis elegans