scholarly journals p24 Proteins and Quality Control of LIN-12 and GLP-1 Trafficking in Caenorhabditis elegans

1999 ◽  
Vol 145 (6) ◽  
pp. 1165-1175 ◽  
Author(s):  
Chenhui Wen ◽  
Iva Greenwald
Keyword(s):  
Quality Control ◽  
Caenorhabditis Elegans ◽  
Control Mechanism ◽  
Genetic Interactions ◽  
C Elegans ◽  
Golgi Transport ◽  
Allele Specific ◽  
Regulation Of Transport ◽  
Quality Control Mechanism ◽  
P24 Proteins

Mutations in the Caenorhabditis elegans sel-9 gene elevate the activity of lin-12 and glp-1, which encode members of the LIN-12/NOTCH family of receptors. Sequence analysis indicates SEL-9 is one of several C. elegans p24 proteins. Allele-specific genetic interactions suggest that reducing sel-9 activity increases the activity of mutations altering the extracellular domains of LIN-12 or GLP-1. Reducing sel-9 activity restores the trafficking to the plasma membrane of a mutant GLP-1 protein that would otherwise accumulate within the cell. Our results suggest a role for SEL-9 and other p24 proteins in the negative regulation of transport of LIN-12 and GLP-1 to the cell surface, and favor a role for p24 proteins in a quality control mechanism for endoplasmic reticulum–Golgi transport.

scholarly journals Misfolded proteins are sorted by a sequential checkpoint mechanism of ER quality control

2004 ◽  
Vol 165 (1) ◽  
pp. 41-52 ◽  
Author(s):  
Shilpa Vashist ◽  
Davis T.W. Ng
Keyword(s):  
Quality Control ◽  
Membrane Proteins ◽  
Control Mechanism ◽  
Degradation Pathway ◽  
Misfolded Proteins ◽  
Er Quality Control ◽  
Golgi Transport ◽  
Test Face ◽  
Folded Proteins ◽  
Quality Control Mechanism

Misfolded proteins retained in the endoplasmic reticulum (ER) are degraded by the ER-associated degradation pathway. The mechanisms used to sort them from correctly folded proteins remain unclear. Analysis of substrates with defined folded and misfolded domains has revealed a system of sequential checkpoints that recognize topologically distinct domains of polypeptides. The first checkpoint examines the cytoplasmic domains of membrane proteins. If a lesion is detected, it is retained statically in the ER and rapidly degraded without regard to the state of its other domains. Proteins passing this test face a second checkpoint that monitors domains localized in the ER lumen. Proteins detected by this pathway are sorted from folded proteins and degraded by a quality control mechanism that requires ER-to-Golgi transport. Although the first checkpoint is obligatorily directed at membrane proteins, the second monitors both soluble and membrane proteins. Our data support a model whereby “properly folded” proteins are defined biologically as survivors that endure a series of distinct checkpoints.

scholarly journals Quality-Control Mechanism for Telomerase RNA Folding in the Cell

Cell Reports ◽  
2020 ◽  
Vol 33 (13) ◽  
pp. 108568
Author(s):  
Xichan Hu ◽  
Jin-Kwang Kim ◽  
Clinton Yu ◽  
Hyun-Ik Jun ◽  
Jinqiang Liu ◽  
...  
Keyword(s):  
Quality Control ◽  
Rna Folding ◽  
Control Mechanism ◽  
Telomerase Rna ◽  
Quality Control Mechanism

Interacting genes required for pharyngeal excitation by motor neuron MC in Caenorhabditis elegans.

Genetics ◽  
1995 ◽  
Vol 141 (4) ◽  
pp. 1365-1382 ◽  
Author(s):  
D M Raizen ◽  
R Y Lee ◽  
L Avery
Keyword(s):  
Caenorhabditis Elegans ◽  
Genetic Interactions ◽  
Neuron Type ◽  
Loss Of Function ◽  
Ach Release ◽  
Pharyngeal Muscle ◽  
Recessive Mutations ◽  
Allele Specific ◽  
Pharyngeal Pumping ◽  
Pumping Rates

Abstract We studied the control of pharyngeal excitation in Caenorhabditis elegans. By laser ablating subsets of the pharyngeal nervous system, we found that the MC neuron type is necessary and probably sufficient for rapid pharyngeal pumping. Electropharyngeograms showed that MC transmits excitatory postsynaptic potentials, suggesting that MC acts as a neurogenic pacemaker for pharyngeal pumping. Mutations in genes required for acetylcholine (ACh) release and an antagonist of the nicotinic ACh receptor (nAChR) reduced pumping rates, suggesting that a nAChR is required for MC transmission. To identify genes required for MC neurotransmission, we screened for mutations that cause slow pumping but no other defects. Mutations in two genes, eat-2 and eat-18, eliminated MC neurotransmission. A gain-of-function eat-18 mutation, ad820sd, and a putative loss-of-function eat-18 mutation, ad1110, both reduced the excitation of pharyngeal muscle in response to the nAChR agonists nicotine and carbachol, suggesting that eat-18 is required for the function of a pharyngeal nAChR. Fourteen recessive mutations in eat-2 fell into five complementation classes. We found allele-specific genetic interactions between eat-2 and eat-18 that correlated with complementation classes of eat-2. We propose that eat-18 and eat-2 function in a multisubunit protein complex involved in the function of a pharyngeal nAChR.

Overexpression of Buffy enhances the loss of parkin and suppresses the loss of Pink1 phenotypes in Drosophila

Genome ◽  
2017 ◽  
Vol 60 (3) ◽  
pp. 241-247
Author(s):  
P. Githure M’Angale ◽  
Brian E. Staveley
Keyword(s):  
Gene Expression ◽  
Quality Control ◽  
Early Onset ◽  
Autosomal Recessive ◽  
Control Mechanism ◽  
Nigrostriatal Neurons ◽  
Climbing Ability ◽  
Quality Control Mechanism ◽  
Locomotor Ability ◽  
Early Onset Parkinson’S Disease

Mutations in parkin (PARK2) and Pink1 (PARK6) are responsible for autosomal recessive forms of early onset Parkinson’s disease (PD). Attributed to the failure of neurons to clear dysfunctional mitochondria, loss of gene expression leads to loss of nigrostriatal neurons. The Pink1/parkin pathway plays a role in the quality control mechanism aimed at eliminating defective mitochondria, and the failure of this mechanism results in a reduced lifespan and impaired locomotor ability, among other phenotypes. Inhibition of parkin or Pink1 through the induction of stable RNAi transgene in the Ddc-Gal4-expressing neurons results in such phenotypes to model PD. To further evaluate the effects of the overexpression of the Bcl-2 homologue Buffy, we analysed lifespan and climbing ability in both parkin-RNAi- and Pink1-RNAi-expressing flies. In addition, the effect of Buffy overexpression upon parkin-induced developmental eye defects was examined through GMR-Gal4-dependent expression. Curiously, Buffy overexpression produced very different effects: the parkin-induced phenotypes were enhanced, whereas the Pink1-enhanced phenotypes were suppressed. Interestingly, the overexpression of Buffy along with the inhibition of parkin in the neuron-rich eye results in the suppression of the developmental eye defects.

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