Faculty Opinions recommendation of SRP keeps polypeptides translocation-competent by slowing translation to match limiting ER-targeting sites.

2008 ◽  
Author(s):  
Davis Ng
Keyword(s):  
Er Targeting

scholarly journals Membrane Topogenesis of a Type I Signal-Anchor Protein, Mouse Synaptotagmin Ii, on the Endoplasmic Reticulum

2000 ◽  
Vol 150 (4) ◽  
pp. 719-730 ◽  
Author(s):  
Yuichiro Kida ◽  
Masao Sakaguchi ◽  
Mitsunori Fukuda ◽  
Katsuhiko Mikoshiba ◽  
Katsuyoshi Mihara
Keyword(s):  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Membrane ◽  
Type I ◽  
Hydrophobic Region ◽  
Anchor Protein ◽  
Nascent Polypeptide ◽  
Charged Residues ◽  
Er Targeting ◽  
Signal Anchor ◽  
Positively Charged

Synaptotagmin II is a type I signal-anchor protein, in which the NH2-terminal domain of 60 residues (N-domain) is located within the lumenal space of the membrane and the following hydrophobic region (H-region) shows transmembrane topology. We explored the early steps of cotranslational integration of this molecule on the endoplasmic reticulum membrane and demonstrated the following: (a) The translocation of the N-domain occurs immediately after the H-region and the successive positively charged residues emerge from the ribosome. (b) Positively charged residues that follow the H-region are essential for maintaining the correct topology. (c) It is possible to dissect the lengths of the nascent polypeptide chains which are required for ER targeting of the ribosome and for translocation of the N-domain, thereby demonstrating that different nascent polypeptide chain lengths are required for membrane targeting and N-domain translocation. (d) The H-region is sufficiently long for membrane integration. (e) Proline residues preceding H-region are critical for N-domain translocation, but not for ER targeting. The proline can be replaced with amino acid with low helical propensity.

scholarly journals A Retention Signal Necessary and Sufficient for Endoplasmic Reticulum Localization Maps to the Transmembrane Domain of Hepatitis C Virus Glycoprotein E2

1998 ◽  
Vol 72 (3) ◽  
pp. 2183-2191 ◽  
Author(s):  
Laurence Cocquerel ◽  
Jean-Christophe Meunier ◽  
André Pillez ◽  
Czeslaw Wychowski ◽  
Jean Dubuisson
Keyword(s):  
Endoplasmic Reticulum ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Transmembrane Domain ◽  
Intracellular Localization ◽  
Native Form ◽  
Glycosyl Phosphatidylinositol ◽  
Er Retention ◽  
Er Targeting ◽  
Necessary And Sufficient

ABSTRACT The hepatitis C virus (HCV) genome encodes two envelope glycoproteins (E1 and E2). These glycoproteins interact to form a noncovalent heterodimeric complex which is retained in the endoplasmic reticulum (ER). To identify whether E1 and/or E2 contains an ER-targeting signal potentially involved in ER retention of the E1-E2 complex, these proteins were expressed alone and their intracellular localization was studied. Due to misfolding of E1 in the absence of E2, no conclusion on the localization of its native form could be drawn from the expression of E1 alone. E2 expressed in the absence of E1 was shown to be retained in the ER similarly to E1-E2 complex. Chimeric proteins in which E2 domains were exchanged with corresponding domains of a protein normally transported to the plasma membrane (CD4) were constructed to identify the sequence responsible for its ER retention. The transmembrane domain (TMD) of E2 (C-terminal 29 amino acids) was shown to be sufficient for retention of the ectodomain of CD4 in the ER compartment. Replacement of the E2 TMD by the anchor signal of CD4 or a glycosyl phosphatidylinositol (GPI) moiety led to its expression on the cell surface. In addition, replacement of the E2 TMD by the anchor signal of CD4 or a GPI moiety abolished the formation of E1-E2 complexes. Together, these results suggest that, besides having a role as a membrane anchor, the TMD of E2 is involved in both complex formation and intracellular localization.

scholarly journals The GET pathway serves to activate Atg32-mediated mitophagy by ER targeting of the Ppg1-Far complex

2021 ◽  
Author(s):  
Mashun Onishi ◽  
Koji Okamoto
Keyword(s):  
Posttranslational Modification ◽  
Scaffold Protein ◽  
Mitochondrial Proteins ◽  
Aaa Atpase ◽  
Selective Autophagy ◽  
Er Targeting ◽  
Additional Loss

AbstractMitophagy removes defective or superfluous mitochondria via selective autophagy. In yeast, the pro-mitophagic protein Atg32 localizes to the mitochondrial surface and interacts with the scaffold protein Atg11 to promote degradation of mitochondria. Although Atg32-Atg11 interactions are thought to be stabilized by Atg32 phosphorylation, how this posttranslational modification is regulated remains obscure. Here we show that cells lacking the guided entry of tail-anchored proteins (GET) pathway exhibit reduced Atg32 phosphorylation and Atg32-Atg11 interactions, which can be rescued by additional loss of the ER-resident Ppg1-Far complex, a multi-subunit phosphatase negatively acting in mitophagy. In GET-deficient cells, Ppg1-Far is predominantly localized to mitochondria. An artificial ER anchoring of Ppg1-Far in GET-deficient cells significantly ameliorates defects in Atg32-Atg11 interactions and mitophagy. Moreover, disruption of GET and Msp1, an AAA-ATPase that extracts non-mitochondrial proteins localized to the mitochondrial surface, elicits synthetic defects in mitophagy. Collectively, we propose that the GET pathway mediates ER targeting of Ppg1-Far, thereby preventing dysregulated suppression of mitophagy activation.

scholarly journals Author response: Retro-2 protects cells from ricin toxicity by inhibiting ASNA1-mediated ER targeting and insertion of tail-anchored proteins

2019 ◽  
Author(s):  
David W Morgens ◽  
Charlene Chan ◽  
Andrew J Kane ◽  
Nicholas R Weir ◽  
Amy Li ◽  
...  
Keyword(s):  
Author Response ◽  
Er Targeting

A New Endoplasmic Reticulum (ER)-Targeting Fluorescent Probe for the Imaging of Cysteine in Living Cells

2020 ◽  
Vol 30 (6) ◽  
pp. 1357-1364
Author(s):  
Lei Zhou ◽  
Yunxia Li ◽  
Aiqin Zhou ◽  
Guanghui Zhang ◽  
Zhi-Qiang Cheng ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Fluorescent Probe ◽  
Living Cells ◽  
Er Targeting

scholarly journals Endoplasmic reticulum targeting fluorescent probes to image mobile Zn2+

2019 ◽  
Vol 10 (47) ◽  
pp. 10881-10887 ◽  
Author(s):  
Le Fang ◽  
Giuseppe Trigiante ◽  
Rachel Crespo-Otero ◽  
Chris S. Hawes ◽  
Michael P. Philpott ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Fluorescent Probes ◽  
Biological Processes ◽  
Er Targeting ◽  
Endoplasmic Reticulum Targeting

Two endoplasmic reticulum (ER) targeting probes were developed to image mobile Zn2+ to help understand Zn2+ related biological processes in the ER.

scholarly journals Physical and Functional Association of the Major Histocompatibility Complex Class I Heavy Chain α3 Domain with the Transporter Associated with Antigen Processing

1998 ◽  
Vol 187 (6) ◽  
pp. 865-874 ◽  
Author(s):  
Kimary Kulig ◽  
Dipankar Nandi ◽  
Igor Bacik ◽  
John J. Monaco ◽  
Stanislav Vukmanovic
Keyword(s):  
Mhc Class Ii ◽  
Heavy Chain ◽  
Antigen Processing ◽  
Surface Expression ◽  
Class I ◽  
Antigenic Peptides ◽  
Histocompatibility Complex ◽  
Cytoplasmic Proteins ◽  
Peptide Loading ◽  
Er Targeting

CD8+ T lymphocytes recognize antigens as short, MHC class I-associated peptides derived by processing of cytoplasmic proteins. The transporter associated with antigen processing translocates peptides from the cytosol into the ER lumen, where they bind to the nascent class I molecules. To date, the precise location of the class I-TAP interaction site remains unclear. We provide evidence that this site is contained within the heavy chain α3 domain. Substitution of a 15 amino acid portion of the H-2Db α3 domain (aa 219-233) with the analogous MHC class II (H-2IAd) β2 domain region (aa 133-147) results in loss of surface expression which can be partially restored upon incubation at 26°C in the presence of excess peptide and β2-microglobulin. Mutant H-2Db (Db219-233) associates poorly with the TAP complex, and cannot present endogenously-derived antigenic peptides requiring TAP-dependent translocation to the ER. However, this presentation defect can be overcome through use of an ER targeting sequence which bypasses TAP-dependent peptide translocation. Thus, the α3 domain serves as an important site of interaction (directly or indirectly) with the TAP complex and is necessary for TAP-dependent peptide loading and class I surface expression.

scholarly journals Regulation of ROS signal transduction by NADPH oxidase 4 localization

2008 ◽  
Vol 181 (7) ◽  
pp. 1129-1139 ◽  
Author(s):  
Kai Chen ◽  
Michael T. Kirber ◽  
Hui Xiao ◽  
Yu Yang ◽  
John F. Keaney
Keyword(s):  
Signal Transduction ◽  
Intracellular Signaling ◽  
Egf Receptor ◽  
Tyrosine Phosphatase ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Diverse Range ◽  
Nadph Oxidase 4 ◽  
Er Targeting ◽  
Ptp 1B ◽  
Egf Signaling

Reactive oxygen species (ROS) function as intracellular signaling molecules in a diverse range of biological processes. However, it is unclear how freely diffusible ROS dictate specific cellular responses. In this study, we demonstrate that nicotinamide adenine dinucleotide phosphate reduced oxidase 4 (Nox4), a major Nox isoform expressed in nonphagocytic cells, including vascular endothelium, is localized to the endoplasmic reticulum (ER). ER localization of Nox4 is critical for the regulation of protein tyrosine phosphatase (PTP) 1B, also an ER resident, through redox-mediated signaling. Nox4-mediated oxidation and inactivation of PTP1B in the ER serves as a regulatory switch for epidermal growth factor (EGF) receptor trafficking and specifically acts to terminate EGF signaling. Consistent with this notion, PTP1B oxidation could also be modulated by ER targeting of antioxidant enzymes but not their untargeted counterparts. These data indicate that the specificity of intracellular ROS-mediated signal transduction may be modulated by the localization of Nox isoforms within specific subcellular compartments.

scholarly journals The Cytoplasmic Tail of GM3 Synthase Defines Its Subcellular Localization, Stability, and In Vivo Activity

2009 ◽  
Vol 20 (13) ◽  
pp. 3088-3100 ◽  
Author(s):  
Satoshi Uemura ◽  
Sayaka Yoshida ◽  
Fumi Shishido ◽  
Jin-ichi Inokuchi
Keyword(s):  
Golgi Apparatus ◽  
Cytoplasmic Tail ◽  
Critical Importance ◽  
Leaky Scanning ◽  
Physiological Conditions ◽  
Gm3 Synthase ◽  
Mrna Variants ◽  
Cytoplasmic Tails ◽  
Er Targeting

GM3 synthase (SAT-I) is the primary glycosyltransferase responsible for the biosynthesis of ganglio-series gangliosides. In this study, we identify three isoforms of mouse SAT-I proteins, named M1-SAT-I, M2-SAT-I, and M3-SAT-I, which possess distinct lengths in their NH2-terminal cytoplasmic tails. These isoforms are produced by leaky scanning from mRNA variants of mSAT-Ia and mSAT-Ib. M2-SAT-I and M3-SAT-I were found to be localized in the Golgi apparatus, as expected, whereas M1-SAT-I was exclusively found in the endoplasmic reticulum (ER). Specific multiple arginines (R) arranged in an R-based motif, RRXXXXR necessary for ER targeting, were found in the cytoplasmic tail of M1-SAT-I, and in vivo GM3 biosynthesis by M1-SAT-I was very low because of restricted transport to the Golgi apparatus. In addition, M1-SAT-I and M3-SAT-I had a long half-life relative to M2-SAT-I. This is the first report demonstrating the presence of an ER-targeting R-based motif in the cytoplasmic tail of a protein in the mammalian glycosyltransferase family of enzymes. The system, which produces SAT-I isoforms having distinct characteristics, is likely to be of critical importance for the regulation of GM3 biosynthesis under various pathological and physiological conditions.

Molecular Cloning of a Novel Ubiquitin-like Protein, UBIN, That Binds to ER Targeting Signal Sequences

2001 ◽  
Vol 280 (2) ◽  
pp. 535-540 ◽  
Author(s):  
Miho Matsuda ◽  
Takaki Koide ◽  
Tetuya Yorihuzi ◽  
Nobuko Hosokawa ◽  
Kazuhiro Nagata
Keyword(s):  
Molecular Cloning ◽  
Signal Sequences ◽  
Er Targeting ◽  
Targeting Signal
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