scholarly journals How many lives does CLIMP-63 have?

2015 ◽  
Vol 43 (2) ◽  
pp. 222-228 ◽  
Author(s):  
Patrick A. Sandoz ◽  
F. Gisou van der Goot
Keyword(s):  
Endoplasmic Reticulum ◽  
Membrane Protein ◽  
Cell Surface ◽  
Transmembrane Protein ◽  
The Other ◽  
Type Ii ◽  
Post Translational Modifications ◽  
Cytosolic Domain ◽  
In Trans

In 1995, in the Biochemical Society Transactions, Mundy published the first review on CLIMP-63 (cytoskeleton-linking membrane protein 63) or CKPA4 (cytoskeleton-associated protein 4), initially just p63 [1]. Here we review the following 20 years of research on this still mysterious protein. CLIMP-63 is a type II transmembrane protein, the cytosolic domain of which has the capacity to bind microtubules whereas the luminal domain can form homo-oligomeric complexes, not only with neighbouring molecules but also, in trans, with CLIMP-63 molecules on the other side of the endoplasmic reticulum (ER) lumen, thus promoting the formation of ER sheets. CLIMP-63 however also appears to have a life at the cell surface where it acts as a ligand-activated receptor. The still rudimentary information of how CLIMP-63 fulfills these different roles, what these are exactly and how post-translational modifications control them, will be discussed.

scholarly journals Retention of a type II surface membrane protein in the endoplasmic reticulum by the Lys-Asp-Glu-Leu sequence.

1992 ◽  
Vol 267 (10) ◽  
pp. 7072-7076
Author(s):  
B.L. Tang ◽  
S.H. Wong ◽  
S.H. Low ◽  
W Hong
Keyword(s):  
Endoplasmic Reticulum ◽  
Membrane Protein ◽  
Surface Membrane ◽  
Type Ii

Intracellular transport of the glycoprotein of VSV is inhibited by CCCP at a late stage of post-translational processing

1989 ◽  
Vol 92 (4) ◽  
pp. 633-642
Author(s):  
J.K. Burkhardt ◽  
Y. Argon
Keyword(s):  
Endoplasmic Reticulum ◽  
Cell Surface ◽  
G Protein ◽  
Vesicular Stomatitis Virus ◽  
Late Stage ◽  
Intracellular Transport ◽  
Post Translational Modifications ◽  
Glycoprotein G ◽  
Golgi Compartment ◽  
Vesicular Stomatitis

The appearance of newly synthesized glycoprotein (G) of vesicular stomatitis virus at the surface of infected BHK cells is inhibited reversibly by treatment with carbonylcyanide m-chlorophenylhydrazone (CCCP). Under the conditions used, CCCP treatment depleted the cellular ATP levels by 40–60%, consistent with inhibition of transport at energy-requiring stages. The G protein that accumulates in cells treated with CCCP is heterogeneous. Most of it is larger than the newly synthesized G protein, is acylated with palmitic acid, and is resistant to endoglycosidase H (Endo H). Most of the arrested G protein is also sensitive to digestion with neuraminidase, indicating that it has undergone at least partial sialylation. A minority of G protein accumulates under these conditions in a less-mature form, suggesting its inability to reach the mid-Golgi compartment. The oligosaccharides of this G protein are Endo-H-sensitive and seem to be partly trimmed. Whereas sialylated G protein was arrested intracellularly, fucose-labelled G protein was able to complete its transport to the cell surface, indicating that a late CCCP-sensitive step separates sialylation from fucosylation. These post-translational modifications indicate that G protein can be transported as far as the trans-Golgi in the presence of CCCP and is not merely arrested in the endoplasmic reticulum.

scholarly journals Efficient endosomal localization of major histocompatibility complex class II-invariant chain complexes requires multimerization of the invariant chain targeting sequence.

1995 ◽  
Vol 129 (5) ◽  
pp. 1217-1228 ◽  
Author(s):  
L S Arneson ◽  
J Miller
Keyword(s):  
Cell Surface ◽  
Class Ii ◽  
Cell Surface Expression ◽  
Invariant Chain ◽  
Antigenic Peptides ◽  
Type Ii ◽  
Wild Type ◽  
Chain Complexes ◽  
Cytosolic Domain ◽  
Localization Signal

During biosynthesis, MHC class II-invariant chain complexes are transported into endosomal compartments where invariant chain (Ii) is degraded and class II encounters antigenic peptides. One of the signals that determines this intracellular transport route has been localized to the cytosolic domain of Ii. Deletion of this signal disrupts endosomal targeting and results in the stable expression of class II-Ii complexes at the surface. In this paper we have examined the role of Ii trimerization on the generation of this endosomal localization signal. In L cell transfectants expressing class II and both wild type Ii and a truncated form of Ii that lacks this endosomal localization signal, Ii was found to form multimers which could contain both wild type and truncated Ii. The multimers were not large aggregates but were found to be discrete complexes, probably the nine molecule class II-Ii complex that has been observed in human B cells. The co-expression of truncated Ii allowed for cell surface expression of a subset of wild type Ii. This surface-expressed wild type Ii associated with truncated Ii in multimers at a 2:1 ratio, indicating that these trimers contain two truncated and one wild type Ii molecule. These data suggest a division in trafficking of Ii trimers: if two wild type Ii molecules are present, the complex is transported to and rapidly degraded in endosomes, whereas the presence of only one wild type Ii results in trafficking and expression of the heterotrimer on the cell surface. Following surface arrival, complexes containing only a single wild type Ii molecule are internalized more rapidly and have a shorter half-life than complexes containing only truncated Ii molecules. These data suggest that although a single Ii cytosolic domain can function as a plasma membrane internalization signal, multimerization of Ii is required for efficient Golgi complex to endosome targeting of class II-Ii complexes.

scholarly journals Autophagosome formation in relation to the endoplasmic reticulum

2020 ◽  
Vol 27 (1) ◽  
Author(s):  
Yo-hei Yamamoto ◽  
Takeshi Noda
Keyword(s):  
Endoplasmic Reticulum ◽  
Membrane Protein ◽  
De Novo ◽  
Transmembrane Protein ◽  
Lipid Transfer ◽  
Membrane Structures ◽  
Autophagosome Formation ◽  
Selective Autophagy ◽  
The Relationship ◽  
Er Membrane

Abstract Autophagy is a process in which a myriad membrane structures called autophagosomes are formed de novo in a single cell, which deliver the engulfed substrates into lysosomes for degradation. The size of the autophagosomes is relatively uniform in non-selective autophagy and variable in selective autophagy. It has been recently established that autophagosome formation occurs near the endoplasmic reticulum (ER). In this review, we have discussed recent advances in the relationship between autophagosome formation and endoplasmic reticulum. Autophagosome formation occurs near the ER subdomain enriched with phospholipid synthesizing enzymes like phosphatidylinositol synthase (PIS)/CDP-diacylglycerol-inositol 3-phosphatidyltransferase (CDIPT) and choline/ethanolamine phosphotransferase 1 (CEPT1). Autophagy-related protein 2 (Atg2), which is involved in autophagosome formation has a lipid transfer capacity and is proposed to directly transfer the lipid molecules from the ER to form autophagosomes. Vacuole membrane protein 1 (VMP1) and transmembrane protein 41b (TMEM41b) are ER membrane proteins that are associated with the formation of the subdomain. Recently, we have reported that an uncharacterized ER membrane protein possessing the DNAJ domain, called ERdj8/DNAJC16, is associated with the regulation of the size of autophagosomes. The localization of ERdj8/DNAJC16 partially overlaps with the PIS-enriched ER subdomain, thereby implying its association with autophagosome size determination.

scholarly journals Cytosolic Phosphorylation of Calnexin Controls Intracellular Ca2+ Oscillations via an Interaction with Serca2b

2000 ◽  
Vol 149 (6) ◽  
pp. 1235-1248 ◽  
Author(s):  
H. Llewelyn Roderick ◽  
James D. Lechleiter ◽  
Patricia Camacho
Keyword(s):  
Endoplasmic Reticulum ◽  
Xenopus Oocytes ◽  
Transmembrane Protein ◽  
Calcium Atpase ◽  
Site Directed Mutagenesis ◽  
Serine Residue ◽  
Endoplasmic Reticulum Calcium ◽  
Inositol 1,4,5 Trisphosphate ◽  
Functional Inhibition ◽  
Cytosolic Domain

Calreticulin (CRT) and calnexin (CLNX) are lectin chaperones that participate in protein folding in the endoplasmic reticulum (ER). CRT is a soluble ER lumenal protein, whereas CLNX is a transmembrane protein with a cytosolic domain that contains two consensus motifs for protein kinase (PK) C/proline- directed kinase (PDK) phosphorylation. Using confocal Ca2+ imaging in Xenopus oocytes, we report here that coexpression of CLNX with sarco endoplasmic reticulum calcium ATPase (SERCA) 2b results in inhibition of intracellular Ca2+ oscillations, suggesting a functional inhibition of the pump. By site-directed mutagenesis, we demonstrate that this interaction is regulated by a COOH-terminal serine residue (S562) in CLNX. Furthermore, inositol 1,4,5-trisphosphate– mediated Ca2+ release results in a dephosphorylation of this residue. We also demonstrate by coimmunoprecipitation that CLNX physically interacts with the COOH terminus of SERCA2b and that after dephosphorylation treatment, this interaction is significantly reduced. Together, our results suggest that CRT is uniquely regulated by ER lumenal conditions, whereas CLNX is, in addition, regulated by the phosphorylation status of its cytosolic domain. The S562 residue in CLNX acts as a molecular switch that regulates the interaction of the chaperone with SERCA2b, thereby affecting Ca2+ signaling and controlling Ca2+-sensitive chaperone functions in the ER.

scholarly journals Endoplasmic reticulum transmembrane protein TMTC3 contributes to O-mannosylation of E-cadherin, cellular adherence, and embryonic gastrulation

2020 ◽  
Vol 31 (3) ◽  
pp. 167-183 ◽  
Author(s):  
Jill B. Graham ◽  
Johan C. Sunryd ◽  
Ketan Mathavan ◽  
Emma Weir ◽  
Ida Signe Bohse Larsen ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Membrane Protein ◽  
Transmembrane Protein ◽  
Homophilic Binding ◽  
Polytopic Membrane Protein ◽  
E Cadherin

Here we characterize TMTC3 as an ER, polytopic membrane protein with C-terminal luminal-facing TPRs, and an O-mannosyltransferase of E-cadherin. O-mannosylation of cadherins by TMTC3 affects cellular adherence, E-cadherin homophilic binding, and embryonic gastrulation, helping to explain the basis of a number of TMTC3-associated disease variants.

scholarly journals Tetraspanins TSP-12 and TSP-14 function redundantly to regulate the trafficking of the type II BMP receptor in Caenorhabditis elegans

2020 ◽  
Vol 117 (6) ◽  
pp. 2968-2977
Author(s):  
Zhiyu Liu ◽  
Herong Shi ◽  
Anthony K. Nzessi ◽  
Anne Norris ◽  
Barth D. Grant ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Cell Surface ◽  
Molecular Mechanisms ◽  
Transmembrane Protein ◽  
Expression Patterns ◽  
Bmp Signaling ◽  
Type I ◽  
Type Ii ◽  
Bmp Receptors

Tetraspanins are a unique family of 4-pass transmembrane proteins that play important roles in a variety of cell biological processes. We have previously shown that 2 paralogous tetraspanins in Caenorhabditis elegans, TSP-12 and TSP-14, function redundantly to promote bone morphogenetic protein (BMP) signaling. The underlying molecular mechanisms, however, are not fully understood. In this study, we examined the expression and subcellular localization patterns of endogenously tagged TSP-12 and TSP-14 proteins. We found that TSP-12 and TSP-14 share overlapping expression patterns in multiple cell types, and that both proteins are localized on the cell surface and in various types of endosomes, including early, late, and recycling endosomes. Animals lacking both TSP-12 and TSP-14 exhibit reduced cell-surface levels of the BMP type II receptor DAF-4/BMPRII, along with impaired endosome morphology and mislocalization of DAF-4/BMPRII to late endosomes and lysosomes. These findings indicate that TSP-12 and TSP-14 are required for the recycling of DAF-4/BMPRII. Together with previous findings that the type I receptor SMA-6 is recycled via the retromer complex, our work demonstrates the involvement of distinct recycling pathways for the type I and type II BMP receptors and highlights the importance of tetraspanin-mediated intracellular trafficking in the regulation of BMP signaling in vivo. As TSP-12 and TSP-14 are conserved in mammals, our findings suggest that the mammalian TSP-12 and TSP-14 homologs may also function in regulating transmembrane protein recycling and BMP signaling.

Man9-Mannosidase from Pig Liver is a Type-II Membrane Protein That Resides in the Endoplasmic Reticulum. cDNA Cloning and Expression of the Enzyme in COS 1 Cells

1997 ◽  
Vol 246 (3) ◽  
pp. 681-689 ◽  
Author(s):  
Erhard Bieberich ◽  
Kornelia Treml ◽  
Christof Volker ◽  
Andreas Rolfs ◽  
Burga Kalz-Fuller ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Membrane Protein ◽  
Cdna Cloning ◽  
Cloning And Expression ◽  
Type Ii ◽  
Pig Liver ◽  
Type Ii Membrane Protein

The fine structure of the developing macrogamete of Eimeria maxima

Parasitology ◽  
1979 ◽  
Vol 79 (2) ◽  
pp. 259-265 ◽  
Author(s):  
R. M. Pittilo ◽  
S. J. Ball
Keyword(s):  
Endoplasmic Reticulum ◽  
Fine Structure ◽  
Parasitophorous Vacuole ◽  
The Other ◽  
Granular Endoplasmic Reticulum ◽  
Type I ◽  
Type Ii ◽  
Eimeria Maxima ◽  
Lipid Inclusions

SUMMARYThe fine structure of the developing macrogamete of Eimeria maxima was studied from chicks killed at intervals from 138 to 147 h after inoculation. The macrogamete developed within a parasitophorous vacuole. Lying within this vacuole and extending for some distance around the periphery of the macrogamete were intravacuolar tubules, grouped in certain areas, and in some cases they were seen to make direct connexions with the cytoplasm of the parasite. During development, electron-pale vesicles were pinched off externally from the surface of the macrogamete. There appeared to be 2 forms of wall-forming bodies of the Type I during development, one form being less osmiophilic than the other. Other organelles present, such as wall-forming bodies of Type II, granular endoplasmic reticulum, mitochondria, canaliculi, lipid inclusions and intravacuolar folds, were similar in structure to those of other Eimeria species.

scholarly journals Endoplasmic reticulum localization of Sec12p is achieved by two mechanisms: Rer1p-dependent retrieval that requires the transmembrane domain and Rer1p-independent retention that involves the cytoplasmic domain.

1996 ◽  
Vol 134 (2) ◽  
pp. 279-293 ◽  
Author(s):  
M Sato ◽  
K Sato ◽  
A Nakano
Keyword(s):  
Transmembrane Domain ◽  
Transmembrane Protein ◽  
Cytoplasmic Domain ◽  
The Other ◽  
Type Ii ◽  
Systematic Analysis ◽  
Transport Vesicles ◽  
Golgi Compartment ◽  
Retention Signal ◽  
Lines Of Evidence

Yeast Sec12p is a type II transmembrane protein in the ER, which is essential for the formation of transport vesicles. From biochemical and morphological lines of evidence, we have proposed that Sec12p is localized to the ER by two mechanisms: static retention in the ER and dynamic retrieval from the early Golgi compartment. We have also shown that Rer1p, a membrane protein in the Golgi, is required for correct localization of Sec12p. In the present study, we have performed a systematic analysis to determine the ER localization signals in Sec12p corresponding to these two mechanisms. Both the transmembrane domain (TMD) and the NH2-terminal cytoplasmic domain of Sec12p show the ability to localize the protein to the ER. The effect of the TMD is potent and sufficient by itself for the ER localization and is strongly dependent on Rer1p. On the other hand, the cytoplasmic domain shows a moderate ER-localization capability which is independent of Rer1p. The rate of mannosyl modification has been measured to distinguish between retention and retrieval. The cytoplasmic domain significantly delays the transport from the ER to the cis-Golgi. In contrast, the TMD shows only a subtle retardation in the transport from the ER to the cis-Golgi but strictly prevents the transport beyond there. From these observations, we conclude that the TMD mainly acts as the retrieval signal and the cytoplasmic domain contains the retention signal. This study not only supports the two-mechanisms hypothesis but also provides powerful tools to dissect the two.

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