scholarly journals trans-Golgi retention of a plasma membrane protein: mutations in the cytoplasmic domain of the asialoglycoprotein receptor subunit H1 result in trans-Golgi retention.

1995 ◽  
Vol 130 (2) ◽  
pp. 285-297 ◽  
Author(s):  
J M Wahlberg ◽  
I Geffen ◽  
F Reymond ◽  
T Simmen ◽  
M Spiess
Keyword(s):  
Cell Surface ◽  
Cytoplasmic Domain ◽  
Asialoglycoprotein Receptor ◽  
Receptor Subunit ◽  
Tubular Structures ◽  
Specific Sequence ◽  
Surface Transport ◽  
Golgi Retention ◽  
Unrelated Sequence ◽  
In Trans

Unlike the wild-type asialoglycoprotein receptor subunit H1 which is transported to the cell surface, endocytosed and recycled, a mutant lacking residues 4-33 of the 40-amino acid cytoplasmic domain was found to be retained intracellularly upon expression in different cell lines. The mutant protein accumulated in the trans-Golgi, as judged from the acquisition of trans-Golgi-specific modifications of the protein and from the immunofluorescence staining pattern. It was localized to juxtanuclear, tubular structures that were also stained by antibodies against galactosyltransferase and gamma-adaptin. The results of further mutagenesis in the cytoplasmic domain indicated that the size rather than the specific sequence of the cytoplasmic domain determines whether H1 is retained in the trans-Golgi or transported to the cell surface. Truncation to less than 17 residues resulted in retention, and extension of a truncated tail by an unrelated sequence restored surface transport. The transmembrane segment of H1 was not sufficient for retention of a reporter molecule and it could be replaced by an artificial apolar sequence without affecting Golgi localization. The cytoplasmic domain thus appears to inhibit interaction(s) of the exoplasmic portion of H1 with trans-Golgi component(s) for example by steric hindrance or by changing the positioning of the protein in the membrane. This mechanism may also be functional in other proteins.

scholarly journals Topological and Structural Plasticity of the Single Ig Fold and the Double Ig Fold Present in CD19

Biomolecules ◽  
2021 ◽  
Vol 11 (9) ◽  
pp. 1290 ◽  
Author(s):  
Philippe Youkharibache
Keyword(s):  
Cell Surface ◽  
3D Structure ◽  
Cell Surface Receptor ◽  
Cell Surface Receptors ◽  
Structural Domain ◽  
Surface Receptors ◽  
Surface Receptor ◽  
In Trans ◽  
In Cis ◽  
Ig Domain

The Ig fold has had a remarkable success in vertebrate evolution, with a presence in over 2% of human genes. The Ig fold is not just the elementary structural domain of antibodies and TCRs, it is also at the heart of a staggering 30% of immunologic cell surface receptors, making it a major orchestrator of cell–cell interactions. While BCRs, TCRs, and numerous Ig-based cell surface receptors form homo- or heterodimers on the same cell surface (in cis), many of them interface as ligand-receptors (checkpoints) on interacting cells (in trans) through their Ig domains. New Ig-Ig interfaces are still being discovered between Ig-based cell surface receptors, even in well-known families such as B7. What is largely ignored, however, is that the Ig fold itself is pseudosymmetric, a property that makes the Ig domain a versatile self-associative 3D structure and may, in part, explain its success in evolution, especially through its ability to bind in cis or in trans in the context of cell surface receptor–ligand interactions. In this paper, we review the Ig domains’ tertiary and quaternary pseudosymmetries, with particular attention to the newly identified double Ig fold in the solved CD19 molecular structure to highlight the underlying fundamental folding elements of Ig domains, i.e., Ig protodomains. This pseudosymmetric property of Ig domains gives us a decoding frame of reference to understand the fold, relate all Ig domain forms, single or double, and suggest new protein engineering avenues.

The NITY motif of the beta-chain cytoplasmic domain is involved in stimulated internalization of the beta3 integrin A isoform

2001 ◽  
Vol 114 (6) ◽  
pp. 1101-1113
Author(s):  
M. Gawaz ◽  
F. Besta ◽  
J. Ylanne ◽  
T. Knorr ◽  
H. Dierks ◽  
...  
Keyword(s):  
Steady State ◽  
Cell Surface ◽  
Molecular Mechanisms ◽  
Chinese Hamster Ovary Cells ◽  
Surface Expression ◽  
Cytoplasmic Domain ◽  
Cell Surface Expression ◽  
Beta Chain ◽  
Single Chain ◽  
Beta3 Integrin

Beta3 integrin adhesion molecules play important roles in wound repair and the regulation of vascular development and three beta3 integrin isoforms (beta3-A, -B, -C) have been described so far. Surface expression of beta3 integrins is dynamically regulated through internalization of beta3 integrins, however, the molecular mechanisms are understood incompletely. To evaluate the role of the cytoplasmic domain of beta3 integrins for internalization, we have generated single chain chimeras with variant and mutated forms of beta3 cytoplasmic domains. Upon transient transfection into chinese hamster ovary cells, it was found that the beta3-A chimera had strongly reduced cell surface expression compared with the corresponding beta3-B, or beta3-C fusion proteins, or the tail-less constructs, whereas steady state levels of all chimeras were near identical. Studies employing cytoplasmic domain mutants showed that the NITY motif at beta3-A 756–759 is critical for plasma membrane expression of beta3-A. Furthermore, delivery of beta3-A to the cell surface was specifically modulated by the cytoplasmic protein beta3-endonexin, a previously described intracellular protein. Coexpression of the native, long form of beta3-endonexin, which does not interact with the beta3 tail, acted as a dominant negative inhibitor of beta3-A-internalization and enhanced steady-state surface expression of the beta3-A-chimera. Furthermore, anti-beta3 antibody-induced internalization of the native beta3 integrin (alpha(IIb)beta3 was dramatically reduced for the Tyr(759)-Ala substitution mutant (alpha(IIb)beta3) (Y759A) and expression of the long isoform of beta3-endonexin substantially decreased the internalization of wild-type alpha(IIb)beta3. Thus, the NITY motif of the beta-chain cytoplasmic domain is involved in stimulated internalization of the beta3 integrin A isoform and beta3-endonexin appears to couple the beta3-A isoform to a specific receptor-recycling pathway.

scholarly journals Intracellular retention of membrane-anchored v-sis protein abrogates autocrine signal transduction.

1992 ◽  
Vol 118 (5) ◽  
pp. 1057-1070 ◽  
Author(s):  
B A Lee ◽  
D J Donoghue
Keyword(s):  
Cell Surface ◽  
Secretory Pathway ◽  
Transmembrane Protein ◽  
Immunofluorescent Localization ◽  
Receptor Ligand ◽  
Surface Transport ◽  
Established Cell ◽  
Autocrine Transformation ◽  
Nih 3T3 ◽  
Retention Signal

An important question regarding autocrine transformation by v-sis is whether intracellularly activated PDGF receptors are sufficient to transform cells or whether activated receptor-ligand complexes are required at the cell surface. We have addressed this question by inhibiting cell surface transport of a membrane-anchored v-sis protein utilizing the ER retention signal of the adenoviral transmembrane protein E3/19K. A v-sis fusion protein containing this signal was retained within the cell and not transported to the cell surface as confirmed by immunofluorescent localization experiments. Also, proteolytic maturation of this protein was suppressed, indicating inefficient transport to post-Golgi compartments of the secretory pathway. When compared with v-sis proteins lacking a functional retention signal, the ER-retained protein showed a diminished ability to transform NIH 3T3 cells, as measured by the number and size of foci formed. In newly established cell lines, the ER-retained protein did not down-regulate PDGF receptors. However, continued passage of these cells selected for a fully transformed phenotype exhibiting downregulated PDGF receptors and proteolytically processed v-sis protein. These results indicate that productive autocrine interactions occur in a post-ER compartment of the secretory pathway. Transport of v-sis protein beyond the Golgi correlated with acquisition of the transformed phenotype. Furthermore, suramin treatment reversed transformation and upregulated the expression of cell surface PDGF receptors, suggesting an important role for receptor-ligand complexes localized to the cell surface.

scholarly journals ADP-Ribosylation Factors Modulate the Cell Surface Transport of G Protein-Coupled Receptors

2010 ◽  
Vol 333 (1) ◽  
pp. 174-183 ◽  
Author(s):  
Chunmin Dong ◽  
Xiaoping Zhang ◽  
Fuguo Zhou ◽  
Huijuan Dou ◽  
Matthew T. Duvernay ◽  
...  
Keyword(s):  
Cell Surface ◽  
G Protein ◽  
G Protein Coupled Receptors ◽  
Surface Transport ◽  
Adp Ribosylation ◽  
G Protein Coupled

scholarly journals Release from Endoplasmic Reticulum Matrix Proteins Controls Cell Surface Transport of MHC Class I Molecules

Traffic ◽  
2015 ◽  
Vol 16 (6) ◽  
pp. 591-603 ◽  
Author(s):  
Susanne Fritzsche ◽  
Esam T. Abualrous ◽  
Britta Borchert ◽  
Frank Momburg ◽  
Sebastian Springer
Keyword(s):  
Endoplasmic Reticulum ◽  
Cell Surface ◽  
Mhc Class I ◽  
Matrix Proteins ◽  
Class I ◽  
Surface Transport ◽  
Mhc Class I Molecules

scholarly journals GABAB Receptor Subunit GB1 at the Cell Surface Independently Activates ERK1/2 through IGF-1R Transactivation

PLoS ONE ◽  
2012 ◽  
Vol 7 (6) ◽  
pp. e39698 ◽  
Author(s):  
Guillaume A. Baloucoune ◽  
Lei Chun ◽  
Wenhua Zhang ◽  
Chanjuan Xu ◽  
Siluo Huang ◽  
...  
Keyword(s):  
Cell Surface ◽  
Gabab Receptor ◽  
Receptor Subunit

scholarly journals The Extracellular Linker of pro-Neuregulin-α2c Is Required for Efficient Sorting and Juxtacrine Function

2007 ◽  
Vol 18 (2) ◽  
pp. 380-393 ◽  
Author(s):  
Juan C. Montero ◽  
Ruth Rodríguez-Barrueco ◽  
Laura Yuste ◽  
Pedro P. Juanes ◽  
Joana Borges ◽  
...  
Keyword(s):  
Biological Activity ◽  
Plasma Membrane ◽  
Cell Surface ◽  
Signal Sequence ◽  
Transmembrane Proteins ◽  
Biologically Active ◽  
Erbb Receptors ◽  
Animal Physiology ◽  
Juxtamembrane Region ◽  
In Trans

The neuregulins (NRGs) play important roles in animal physiology, and their disregulation has been linked to diseases such as cancer or schizophrenia. The NRGs may be produced as transmembrane proteins (proNRGs), even though they lack an N-terminal signal sequence. This raises the question of how NRGs are sorted to the plasma membrane. It is also unclear whether in their transmembrane state, the NRGs are biologically active. During studies aimed at solving these questions, we found that deletion of the extracellular juxtamembrane region termed the linker, decreased cell surface exposure of the mutant proNRGΔLinker, and caused its entrapment at the cis-Golgi. We also found that cell surface–exposed transmembrane NRG forms retain biological activity. Thus, a mutant whose cleavage is impaired but is correctly sorted to the plasma membrane activated ErbB receptors in trans and also stimulated proliferation. Because the linker is implicated in surface sorting and the regulation of the cleavage of transmembrane NRGs, our data indicate that this region exerts multiple important roles in the physiology of NRGs.

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