PubMed Health⌕ Search
Home/Archive/PubMed

PubMed · 12361587

ER quality control: a function for sugars in the cytosol.

J Michael Lord·Lorenzo Frigerio
View original source ↗Export metadata ↓

Abstract

Misfolded glycoproteins in the endoplasmic reticulum of a eukaryotic cell are exported to the cytosol, where they are proteolytically degraded by the ubiquitin-proteasome system. A recent study has identified a novel E3 ubiquitin ligase that recognises target glycoproteins via their sugar moieties.

Explore related subjects

CytosolEndoplasmic ReticulumGlycoproteinsLigasesProtein FoldingUbiquitinUbiquitin-Protein LigasesJournal Article

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

J Michael Lord, Lorenzo Frigerio. 2002-10-01. ER quality control: a function for sugars in the cytosol.. https://doi.org/10.1016/s0960-9822(02)01162-4

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

PubMed2006

Cytosolic factor- and TOM-independent import of C-tail-anchored mitochondrial outer membrane proteins.

C-tail-anchored (C-TA) proteins are anchored to specific organelle membranes by a single transmembrane segment (TMS) at the C-terminus, extruding the N-terminal functional domains into the cytoplasm in which the TMS and following basic segment function as the membrane-targeting signals. Here, we analyzed the import route of mitochondrial outer membrane (MOM) C-TA proteins, Bak, Bcl-XL, and Omp25, using digitonin-permeabilized HeLa cells, which provide specific and efficient import under competitive conditions. These experiments revealed that (i) C-TA proteins were imported to the MOM through a common pathway independent of the components of the preprotein translocase of the outer membrane, (ii) the C-TA protein-targeting signal functioned autonomously in the absence of cytoplasmic factors that specifically recognize the targeting signals and deliver the preproteins to the MOM, (iii) the function of a cytoplasmic chaperone was required if the cytoplasmic domains of the C-TA proteins assumed an import-incompetent conformation, and intriguingly, (iv) the MOM-targeting signal of Bak, in the context of the Bak molecule, required activation by the interaction of its cytoplasmic domain with VDAC2 before MOM targeting.

Cytosol↗
PubMed2006

The interplay between discrete noise and nonlinear chemical kinetics in a signal amplification cascade.

We used various analytical and numerical techniques to elucidate signal propagation in a small enzymatic cascade which is subjected to external and internal noises. The nonlinear character of catalytic reactions, which underlie protein signal transduction cascades, renders stochastic signaling dynamics in cytosol biochemical networks distinct from the usual description of stochastic dynamics in gene regulatory networks. For a simple two-step enzymatic cascade which underlies many important protein signaling pathways, we demonstrated that the commonly used techniques such as the linear noise approximation and the Langevin equation become inadequate when the number of proteins becomes too low. Consequently, we developed a new analytical approximation, based on mixing the generating function and distribution function approaches, to the solution of the master equation that describes nonlinear chemical signaling kinetics for this important class of biochemical reactions. Our techniques work in a much wider range of protein number fluctuations than the methods used previously. We found that under certain conditions the burst phase noise may be injected into the downstream signaling network dynamics, resulting possibly in unusually large macroscopic fluctuations. In addition to computing first and second moments, which is the goal of commonly used analytical techniques, our new approach provides the full time-dependent probability distributions of the colored non-Gaussian processes in a nonlinear signal transduction cascade.

Cytosol↗
PubMed2006

2-color photobleaching experiments reveal distinct intracellular dynamics of two components of the Hsp90 complex.

The abundant molecular chaperone Hsp90 functions in association with co-chaperones including p23 to promote the folding and maturation of a subset of cytosolic proteins. "Fluorescence recovery after photobleaching" (FRAP) experiments showed that the dynamics of p23 in live cells is dictated by Hsp90. Since Hsp90 is present in large excess over p23, the mobility of Hsp90 could conceivably be quite different. To facilitate the analysis and to allow a direct comparison with p23, we developed a 2-color FRAP technique. Two test proteins are expressed as fusion proteins with the two spectrally separable fluorescent proteins mCherry and enhanced green fluorescent protein (EGFP). The 2-color FRAP technique is powerful for the concomitant recording of two proteins located in the same area of a cell, two components of the same protein complex, or mutant and wild-type versions of the same protein under identical experimental conditions. 2-color FRAP of Hsp90 and p23 is virtually indistinguishable, consistent with the notion that they are both engaged in a multitude of large protein complexes. However, when Hsp90-p23 complexes are disrupted by the Hsp90 inhibitor geldanamycin, p23 moves by free diffusion while Hsp90 maintains its low mobility because it remains bound in remodeled multicomponent complexes.

Cytosol↗