Z-membranes: artificial organelles for overexpressing recombinant integral membrane proteins.

Gong, Fangcheng; Giddings, T. H.; Meehl, Janet B.; Staehelin, L. Andrew

doi:10.1073/pnas.93.5.2219

Cited by 43 publications

(53 citation statements)

References 28 publications

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“…Although the molecular details remain to be discovered, our results suggest that proper folding of the Hmg1p membrane domain is a critical first step in the karmellae signaling process and indicate that this folding may be influenced by sequences at the carboxyl terminus. Our results also rule out models that suggest that oligomerization of a membrane protein is sufficient to induce alterations in membrane assembly (Gong et al, 1996). Consequently, identifying trans-acting factors that respond to the Hmg1p membrane domain will be essential for learning how this protein stimulates the dramatic changes in membrane biogenesis and organization that accompany karmellae assembly.…”

Section: Discussionmentioning

confidence: 55%

“…Cheng and coworkers (1999) did not analyze the ability of their fusion proteins to induce crystalloid ER. However, studies of microsomal aldehyde dehydrogenase, which induces crystalloid ER similar to that induced by HMG-CoA reductase, also indicate the importance of interactions via the carboxyl termini for induction of membrane assembly (Masaki et al, 1994Gong et al, 1996;Yamamoto et al, 1996). Cheng et al (1999) propose that dimerization via the HMG-CoA reductase catalytic domains serves to promote or to stabilize interactions between the attached membrane domains.…”

Section: Discussionmentioning

confidence: 99%

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The Role of the 3-Hydroxy 3-Methylglutaryl Coenzyme A Reductase Cytosolic Domain in Karmellae Biogenesis

Profant¹,

Roberts

Koning

et al. 1999

MBoC

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In all cells examined, specific endoplasmic reticulum (ER) membrane arrays are induced in response to increased levels of the ER membrane protein 3-hydroxy 3-methylglutaryl coenzyme A (HMG-CoA) reductase. In yeast, expression of Hmg1p, one of two yeast HMG-CoA reductase isozymes, induces assembly of nuclear-associated ER stacks called karmellae. Understanding the features of HMG-CoA reductase that signal karmellae biogenesis would provide useful insights into the regulation of membrane biogenesis. The HMG-CoA reductase protein consists of two domains, a multitopic membrane domain and a cytosolic catalytic domain. Previous studies had indicated that the HMG-CoA reductase membrane domain was exclusively responsible for generation of ER membrane proliferations. Surprisingly, we discovered that this conclusion was incorrect: sequences at the carboxyl terminus of HMG-CoA reductase can profoundly affect karmellae biogenesis. Specifically, truncations of Hmg1p that removed or shortened the carboxyl terminus were unable to induce karmellae assembly. This result indicated that the membrane domain of Hmg1p was not sufficient to signal for karmellae assembly. Using β-galactosidase fusions, we demonstrated that the carboxyl terminus was unlikely to simply serve as an oligomerization domain. Our working hypothesis is that a truncated or misfolded cytosolic domain prevents proper signaling for karmellae by interfering with the required tertiary structure of the membrane domain.

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Section: Discussionmentioning

confidence: 55%

Section: Discussionmentioning

confidence: 99%

The Role of the 3-Hydroxy 3-Methylglutaryl Coenzyme A Reductase Cytosolic Domain in Karmellae Biogenesis

Profant¹,

Roberts

Koning

et al. 1999

MBoC

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“…A number of studies have implicated head-to-head dimerization of the cytosolic domains of overexpressed ER membrane proteins in cisternal stacking [49][50][51][52][53]. In the study of Snapp et al, this hypothesis was directly tested.…”

Section: Smooth Ermentioning

confidence: 99%

Endoplasmic reticulum architecture: structures in flux

Borgese

Francolini

Snapp

2006

Current Opinion in Cell Biology

203

147

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The endoplasmic reticulum (ER) is a dynamic pleiomorphic organelle containing continuous but distinct subdomains. The diversity of ER structures parallels its many functions, including secretory protein biogenesis, lipid synthesis, drug metabolism and Ca 2+ signaling. Recent studies are revealing how elaborate ER structures arise in response to subtle changes in protein levels, dynamics, and interactions as well as in response to alterations in cytosolic ion concentrations. Subdomain formation appears to be governed by principles of self-organization. Once formed, ER subdomains remain malleable and can be rapidly transformed into alternative structures in response to altered conditions. The mechanisms that modulate ER structure are likely to be important for the generation of the characteristic shapes of other organelles.

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“…It has been proposed that proteins that regulate lipid metabolism, such as HMG-CoA reductase, induce the formation of these structures because of the extensive requirement of membrane biogenesis. However, subsequent studies suggested that the oligomerization state of the ER integral membrane proteins is crucial for their production (7,13,14).The organization of the ER is also sensitive to drugs that induce microtubule depolymerization, such as colchicine or nocodazole. These drugs cause retraction of the ER tubules from the cell periphery and consequently, the formation of ER membrane aggregates around the nucleus.…”

mentioning

confidence: 99%

mentioning

confidence: 99%

Differential Regulation of Endoplasmic Reticulum Structure through VAP-Nir Protein Interaction

Amarilio

Ramachandran

Sabanay

et al. 2005

Journal of Biological Chemistry

178

161

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The endoplasmic reticulum (ER) exhibits a characteristic tubular structure that is dynamically rearranged in response to specific physiological demands. However, the mechanisms by which the ER maintains its characteristic structure are largely unknown. Here we show that the integral ER-membrane protein VAP-B causes a striking rearrangement of the ER through interaction with the Nir2 and Nir3 proteins. We provide evidence that Nir (Nir1, Nir2, and Nir3)-VAP-B interactions are mediated through the conserved FFAT (two phenylalanines (FF) in acidic tract) motif present in Nir proteins. However, each interaction affects the structural integrity of the ER differently. Whereas the Nir2-VAP-B interaction induces the formation of stacked ER membrane arrays, the Nir3-VAP-B interaction leads to a gross remodeling of the ER and the bundling of thick microtubules along the altered ER membranes. In contrast, the Nir1-VAP-B interaction has no apparent effect on ER structure. We also show that the Nir2-VAP-B interaction attenuates protein export from the ER. These results demonstrate new mechanisms for the regulation of ER structure, all of which are mediated through interaction with an identical integral ER-membrane protein. The endoplasmic reticulum (ER)1 is an extensive network of membranes comprised of an array of interconnecting tubules and cisternae that emerges from the nuclear envelope (NE) and extends peripherally throughout the cell cytoplasm (1). It contains several structurally distinct domains, including the NE, the rough and smooth ER (rER and sER), and the regions that contact other organelles, such as the Golgi apparatus, the late endosomes, the lysosomes, mitochondria, peroxisomes, and the plasma membrane (2). The ER functions in diverse metabolic processes including lipid synthesis, carbohydrate metabolism, and the detoxification of drugs. It is responsible for the synthesis, translocation, glycosylation, folding, assembly, and processing of secretory and membrane proteins, and it functions in intracellular calcium storage and sequestering (3, 4).While the function of the ER in membrane trafficking, lipid biosynthesis, and calcium signaling have been extensively studied, the mechanism by which the ER maintains its characteristic structure in vivo remains largely unknown. Studies from yeast and mammalian cells have shown that the size and/or structure of the ER is extremely sensitive to certain cellular stress conditions, such as the unfolded protein response (UPR) or to the overexpression of a subset of ERresident membrane proteins (5, 6). Overexpression of 3-hydroxymethyl-3-methylglutaryl coenzyme A (HMG-CoA) reductase, microsomal aldehyde dehydrogenase (msALDH), cytochrome P-450, and malfolded cytochrome P-450, causes the proliferation of ER membranes and stacking of the ER cisternae into organized structures known as crystalloid ER, sinusoidal ER, or karmellae (7-12). The formation of these structures is easily visible and can be used as a quantitative method for studying ER membrane biogenesis (5). Neverth...

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Z-membranes: artificial organelles for overexpressing recombinant integral membrane proteins.

Cited by 43 publications

References 28 publications

The Role of the 3-Hydroxy 3-Methylglutaryl Coenzyme A Reductase Cytosolic Domain in Karmellae Biogenesis

The Role of the 3-Hydroxy 3-Methylglutaryl Coenzyme A Reductase Cytosolic Domain in Karmellae Biogenesis

Endoplasmic reticulum architecture: structures in flux

Differential Regulation of Endoplasmic Reticulum Structure through VAP-Nir Protein Interaction

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