Faculty Opinions recommendation of C. elegans PAT-6/actopaxin plays a critical role in the assembly of integrin adhesion complexes in vivo.

2003 ◽  
Author(s):  
Jean Schwarzbauer
Keyword(s):  
Critical Role ◽  
C Elegans

scholarly journals Sequence and transmembrane topology of MEC-4, an ion channel subunit required for mechanotransduction in Caenorhabditis elegans.

1996 ◽  
Vol 133 (5) ◽  
pp. 1071-1081 ◽  
Author(s):  
C C Lai ◽  
K Hong ◽  
M Kinnell ◽  
M Chalfie ◽  
M Driscoll
Keyword(s):  
Caenorhabditis Elegans ◽  
Ion Channel ◽  
Critical Role ◽  
Comparative Sequence Analysis ◽  
Mechanical Stimuli ◽  
Transmembrane Topology ◽  
C Elegans ◽  
Carboxy Terminal

The process by which mechanical stimuli are converted into cellular responses is poorly understood, in part because key molecules in this mode of signal transduction, the mechanically gated ion channels, have eluded cloning efforts. The Caenorhabditis elegans mec-4 gene encodes a subunit of a candidate mechanosensitive ion channel that plays a critical role in touch reception. Comparative sequence analysis of C. elegans and Caenorhabditis briggsae mec-4 genes was used to initiate molecular studies that establish MEC-4 as a 768-amino acid protein that includes two hydrophobic domains theoretically capable of spanning a lipid bilayer. Immunoprecipitation of in vitro translated mec-4 protein with domain-specific anti-MEC-4 antibodies and in vivo characterization of a series of mec-4lacZ fusion proteins both support the hypothesis that MEC-4 crosses the membrane twice. The MEC-4 amino- and carboxy-terminal domains are situated in the cytoplasm and a large domain, which includes three Cys-rich regions, is extracellular. Definition of transmembrane topology defines regions that might interact with the extracellular matrix or cytoskeleton to mediate mechanical signaling.

scholarly journals Eps15 membrane-binding and -bending activity acts redundantly with Fcho1 during clathrin-mediated endocytosis

2016 ◽  
Vol 27 (17) ◽  
pp. 2675-2687 ◽  
Author(s):  
Lei Wang ◽  
Adam Johnson ◽  
Michael Hanna ◽  
Anjon Audhya
Keyword(s):  
Genetic Interaction ◽  
Critical Role ◽  
Membrane Binding ◽  
Accessory Proteins ◽  
Membrane Remodeling ◽  
Bar Domain ◽  
C Elegans ◽  
Accessory Factor

Clathrin coat assembly on membranes requires cytosolic adaptors and accessory proteins, which bridge triskeleons with the lipid bilayer and stabilize lattice architecture throughout the process of vesicle formation. In Caenorhabditis elegans, the prototypical AP-2 adaptor complex, which is activated by the accessory factor Fcho1 at the plasma membrane, is dispensable during embryogenesis, enabling us to define alternative mechanisms that facilitate clathrin-mediated endocytosis. Here we uncover a synthetic genetic interaction between C. elegans Fcho1 (FCHO-1) and Eps15 (EHS-1), suggesting that they function in a parallel and potentially redundant manner. Consistent with this idea, we find that the FCHO-1 EFC/F-BAR domain and the EHS-1 EH domains exhibit highly similar membrane-binding and -bending characteristics in vitro. Furthermore, we demonstrate a critical role for EHS-1 when FCHO-1 membrane-binding and -bending activity is specifically eliminated in vivo. Taken together, our data highlight Eps15 as an important membrane-remodeling factor, which acts in a partially redundant manner with Fcho proteins during the earliest stages of clathrin-mediated endocytosis.

scholarly journals Engineering a conserved RNA regulatory protein repurposes its biological function in vivo

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Vandita D Bhat ◽  
Kathleen L McCann ◽  
Yeming Wang ◽  
Dallas R Fonseca ◽  
Tarjani Shukla ◽  
...  
Keyword(s):  
Genome Engineering ◽  
Rna Binding ◽  
Biological Function ◽  
Rna Binding Proteins ◽  
Critical Role ◽  
Regulatory Protein ◽  
Motif Length ◽  
C Elegans ◽  
Preferential Binding

PUF (PUmilio/FBF) RNA-binding proteins recognize distinct elements. In C. elegans, PUF-8 binds to an 8-nt motif and restricts proliferation in the germline. Conversely, FBF-2 recognizes a 9-nt element and promotes mitosis. To understand how motif divergence relates to biological function, we first determined a crystal structure of PUF-8. Comparison of this structure to that of FBF-2 revealed a major difference in a central repeat. We devised a modified yeast 3-hybrid screen to identify mutations that confer recognition of an 8-nt element to FBF-2. We identified several such mutants and validated structurally and biochemically their binding to 8-nt RNA elements. Using genome engineering, we generated a mutant animal with a substitution in FBF-2 that confers preferential binding to the PUF-8 element. The mutant largely rescued overproliferation in animals that spontaneously generate tumors in the absence of puf-8. This work highlights the critical role of motif length in the specification of biological function.

scholarly journals C. elegans PAT-6/Actopaxin Plays a Critical Role in the Assembly of Integrin Adhesion Complexes In Vivo

2003 ◽  
Vol 13 (11) ◽  
pp. 922-932 ◽  
Author(s):  
Xinyi Lin ◽  
Hiroshi Qadota ◽  
Donald G. Moerman ◽  
Benjamin D. Williams
Keyword(s):  
Critical Role ◽  
C Elegans

scholarly journals Effects of High Dietary Carbohydrate and Lipid Intake on the Lifespan of C. elegans

Cells ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 2359
Author(s):  
Berenice Franco-Juárez ◽  
Saúl Gómez-Manzo ◽  
Beatriz Hernández-Ochoa ◽  
Noemi Cárdenas-Rodríguez ◽  
Roberto Arreguin-Espinosa ◽  
...  
Keyword(s):  
High Glucose ◽  
Molecular Mechanisms ◽  
Critical Role ◽  
In Vivo Model ◽  
C Elegans ◽  
Age Related ◽  
Dietary Nutrients ◽  
High Lipid ◽  
Induced Changes

Health and lifespan are influenced by dietary nutrients, whose balance is dependent on the supply or demand of each organism. Many studies have shown that an increased carbohydrate–lipid intake plays a critical role in metabolic dysregulation, which impacts longevity. Caenorhabditis elegans has been successfully used as an in vivo model to study the effects of several factors, such as genetic, environmental, diet, and lifestyle factors, on the molecular mechanisms that have been linked to healthspan, lifespan, and the aging process. There is evidence showing the causative effects of high glucose on lifespan in different diabetic models; however, the precise biological mechanisms affected by dietary nutrients, specifically carbohydrates and lipids, as well as their links with lifespan and longevity, remain unknown. Here, we provide an overview of the deleterious effects caused by high-carbohydrate and high-lipid diets, as well as the molecular signals that affect the lifespan of C. elegans; thus, understanding the detailed molecular mechanisms of high-glucose- and lipid-induced changes in whole organisms would allow the targeting of key regulatory factors to ameliorate metabolic disorders and age-related diseases.

scholarly journals Ribosomal ubiquitination facilitates mRNA cleavage and ribosome rescue during No-Go and Nonstop mRNA Decay

2021 ◽  
Author(s):  
Parissa C. Monem ◽  
Audrey L. Piatt ◽  
Nitin Vidyasagar ◽  
Marissa L. Glover ◽  
Thea A. Egelhofer ◽  
...  
Keyword(s):  
Ribosomal Proteins ◽  
Mrna Decay ◽  
Critical Role ◽  
Mrna Degradation ◽  
C Elegans ◽  
N Terminus ◽  
Nonstop Mrna Decay ◽  
Cellular Machinery ◽  
Translation Signals

During translational surveillance, ribosomes play a critical role in detecting problematic mRNAs and signaling cellular machinery to repress the offending messages. Prior work has shown that problematic mRNAs identified by two surveillance pathways (Nonstop and No-Go mRNA Decay) are detected by ribosome collisions and subsequent ribosomal ubiquitination, yet how ribosomal ubiquitination leads to repression has remained unclear. Here, we deploy C. elegans to unravel the series of coordinated events during Nonstop and No-Go mRNA Decay. We probe the metazoan SKI RNA helicase complex to uncover functionally significant residues and reveal divergence of the SKI-exosome interface. We define a functional requirement for ubiquitination on at least two ribosomal proteins during No-Go mRNA Decay, and illustrate how ubiquitination recruits the endonuclease NONU-1 via CUE domains and the ribosome rescue factor HBS-1 via its poorly characterized N-terminus. Our molecular characterization (1) underscores the importance of ribosomal ubiquitination in mRNA degradation, (2) shows similar and distinct genetic dependencies of factors in Nonstop and No-Go mRNA Decay, and (3) uncovers a conspicuous absence of distinct ribosomal stalls at No-Go mRNA Decay substrates. Our work demonstrates mechanisms by which translation signals to effectors of co-translational mRNA repression and has implications for the study of translation and ribosomal species in vivo.

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