Tail-anchored protein biosynthesis at the endoplasmic reticulum: the same but different

2004 ◽  
Vol 32 (5) ◽  
pp. 659-662 ◽  
Author(s):  
S. High ◽  
B.M. Abell
Keyword(s):  
Endoplasmic Reticulum ◽  
Molecular Basis ◽  
Protein Biosynthesis ◽  
Cytochrome B5 ◽  
Membrane Insertion ◽  
Essential Step ◽  
Protein Biogenesis ◽  
Multiple Routes ◽  
Membrane Components ◽  
Cytosolic Factors

The post-translational integration of tail-anchored proteins at the endoplasmic reticulum represents a novel and distinct pathway for membrane protein synthesis. Studies of various precursors, exemplified by the synaptobrevins and cytochrome b5, indicate that multiple routes may facilitate their biosynthesis. There is clear evidence that both cytosolic factors and membrane components facilitate the efficient membrane insertion of at least some tail-anchored proteins. However, the nature of these mediators is currently unknown and their identification will be an essential step in defining the molecular basis of tail-anchored protein biogenesis.

scholarly journals A biochemical analysis of the constraints of tail-anchored protein biogenesis

2011 ◽  
Vol 436 (3) ◽  
pp. 719-727 ◽  
Author(s):  
Pawel Leznicki ◽  
Jim Warwicker ◽  
Stephen High
Keyword(s):  
Transmembrane Domain ◽  
Cytochrome B5 ◽  
Energetic Cost ◽  
Tetratricopeptide Repeat ◽  
Membrane Insertion ◽  
Endoplasmic Reticulum Membrane ◽  
Protein Biogenesis ◽  
Covalent Modifications ◽  
Poly Ethylene ◽  
Ta Proteins

TA (tail-anchored) proteins utilize distinct biosynthetic pathways, including TRC40 (transmembrane domain recognition complex of 40 kDa)-mediated, chaperone-dependent and/or unassisted routes to the ER (endoplasmic reticulum) membrane. We have addressed the flexibility of cytosolic components participating in these pathways, and explored the thermodynamic constraints of their membrane insertion, by exploiting recombinant forms of Sec61β and Cytb5 (cytochrome b5) bearing covalent modifications within their TA region. In both cases, efficient membrane insertion relied on cytosolic factors capable of accommodating a surprising range of covalent modifications to the TA region. For Sec61β, we found that both SGTA (small glutamine-rich tetratricopeptide repeat-containing protein α) and TRC40 can bind this substrate with a singly PEGylated TA region. However, by introducing two PEG [poly(ethylene glycol)] moieties, TRC40 binding can be prevented, resulting in a block of subsequent membrane integration. Although TRC40 can bind Sec61β polypeptides singly PEGylated at different locations, membrane insertion is more sensitive to the precise location of PEG attachment. Modelling and experimentation indicate that this post-TRC40 effect results from an increased energetic cost of inserting different PEGylated TA regions into the lipid bilayer. We therefore propose that the membrane integration of TA proteins delivered via TRC40 is strongly dependent upon underlying thermodynamics, and speculate that their insertion is via a phospholipid-mediated process.

scholarly journals Growth of the nuclear envelope in the vegetative phase of the green alga Acetabularia. Evidence for assembly from membrane components synthesized in the cytoplasm.

1975 ◽  
Vol 66 (3) ◽  
pp. 681-689 ◽  
Author(s):  
W W Franke ◽  
H Spring ◽  
U Scheer ◽  
H Zerban
Keyword(s):  
Endoplasmic Reticulum ◽  
Nuclear Envelope ◽  
Green Alga ◽  
Special Form ◽  
Vegetative Phase ◽  
Primary Nucleus ◽  
Membrane Components

The primary nucleus of the green alga Acetabularia grows about 25,000-fold in volume while it is separated from the endoplasmic reticulum and the whole cytoplasm by a special paranuclear cisterna of a vacuolar labyrinthum system which shows only very few (two to six per square micrometer) and small (ca. 40-120 nm in diamter) fenestrations. The nuclear envelope does not bear polyribosomes, nor do they occur in the entire zone intermediate between the nuclear envelope and the paranuclear cisterna. It is suggested that this special form of nuclear envelope growth takes place by assembly from cytoplasmically synthesized proteins that are translocated across the paranuclear cisterna in a nonmembrane-structured form.

Membrane-protein biosynthesis at the endoplasmic reticulum

1999 ◽  
Vol 27 (6) ◽  
pp. 883-888 ◽  
Author(s):  
Stephen High ◽  
Julie J. A. Greenfield ◽  
Suzanna L. Meacock ◽  
Jason D. Oliver
Keyword(s):  
Endoplasmic Reticulum ◽  
Membrane Protein ◽  
Protein Biosynthesis

scholarly journals Quantitative Proteomics and Lipidomics Analysis of Endoplasmic Reticulum of Macrophage Infected with Mycobacterium tuberculosis

2015 ◽  
Vol 2015 ◽  
pp. 1-13 ◽  
Author(s):  
Najmuddin Mohd Saquib ◽  
Shilpa Jamwal ◽  
Mukul Kumar Midha ◽  
Hirdya Narain Verma ◽  
Venkatasamy Manivel
Keyword(s):  
Endoplasmic Reticulum ◽  
Cell Biology ◽  
Molecular Basis ◽  
Quantitative Proteomics ◽  
Host Response ◽  
Mycobacterial Infection ◽  
Cholesterol Homeostasis ◽  
Functional Attributes ◽  
Rough Er ◽  
The Impact

Even though endoplasmic reticulum (ER) stress associated with mycobacterial infection has been well studied, the molecular basis of ER as a crucial organelle to determine the fate of Mtb is yet to be established. Here, we have studied the ability of Mtb to manipulate the ultrastructural architecture of macrophage ER and found that the ER-phenotypes associated with virulent (H37Rv) and avirulent (H37Ra) strains were different: a rough ER (RER) with the former against a smooth ER (SER) with the later. Further, the functional attributes of these changes were probed by MS-based quantitative proteomics (133 ER proteins) and lipidomics (8 phospholipids). Our omics approaches not only revealed the host pathogen cross-talk but also emphasized how precisely Mtb uses proteins and lipids in combination to give rise to characteristic ER-phenotypes. H37Ra-infected macrophages increased the cytosolic Ca2+ levels by attenuating the ATP2A2 protein and simultaneous induction of PC/PE expression to facilitate apoptosis. However, H37Rv inhibited apoptosis and further controlled the expression of EST-1 and AMRP proteins to disturb cholesterol homeostasis resulting in sustained infection. This approach offers the potential to decipher the specific roles of ER in understanding the cell biology of mycobacterial infection with special reference to the impact of host response.

scholarly journals The C-terminus of cytochrome b5 confers endoplasmic reticulum specificity by preventing spontaneous insertion into membranes

2007 ◽  
Vol 401 (3) ◽  
pp. 701-709 ◽  
Author(s):  
Matthew P. A. Henderson ◽  
Yeen Ting Hwang ◽  
John M. Dyer ◽  
Robert T. Mullen ◽  
David W. Andrews
Keyword(s):  
Endoplasmic Reticulum ◽  
Subcellular Localization ◽  
Lipid Bilayers ◽  
Fusion Proteins ◽  
Molecular Mechanisms ◽  
Cytochrome B5 ◽  
Terminal Sequence ◽  
C Terminus

The molecular mechanisms that determine the correct subcellular localization of proteins targeted to membranes by tail-anchor sequences are poorly defined. Previously, we showed that two isoforms of the tung oil tree [Vernicia (Aleurites) fordii] tail-anchored Cb5 (cytochrome b5) target specifically to ER (endoplasmic reticulum) membranes both in vivo and in vitro [Hwang, Pelitire, Henderson, Andrews, Dyer and Mullen (2004) Plant Cell 16, 3002–3019]. In the present study, we examine the targeting of various tung Cb5 fusion proteins and truncation mutants to purified intracellular membranes in vitro in order to assess the importance of the charged CTS (C-terminal sequence) in targeting to specific membranes. Removal of the CTS from tung Cb5 proteins resulted in efficient binding to both ER and mitochondria. Results from organelle competition, liposome-binding and membrane proteolysis experiments demonstrated that removal of the CTS results in spontaneous insertion of tung Cb5 proteins into lipid bilayers. Our results indicate that the CTSs from plant Cb5 proteins provide ER specificity by preventing spontaneous insertion into incorrect subcellular membranes.

scholarly journals A Network of Cytosolic Factors Targets SRP-Independent Proteins to the Endoplasmic Reticulum

Cell ◽  
2013 ◽  
Vol 152 (5) ◽  
pp. 1134-1145 ◽  
Author(s):  
Tslil Ast ◽  
Galit Cohen ◽  
Maya Schuldiner
Keyword(s):  
Endoplasmic Reticulum ◽  
Cytosolic Factors
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