Exit of newly synthesized membrane proteins from the trans cisterna of the Golgi complex to the plasma membrane.

Griffiths, Gareth; Pfeiffer, S. E.; Simons, Kai; Matlin, Karl S.

doi:10.1083/jcb.101.3.949

Cited by 409 publications

(317 citation statements)

References 41 publications

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“…The 20°C incubation produces a block in post-Golgi transport such that newly synthesized proteins accumulate in the Golgi (Matlin and Simons, 1983;Griffiths et al, 1985;Saraste et al, 1986;our unpublished data). Although only 30% of APN was detected in its mature form after the 2 h block (0 min after release), ϳ25% of that population was detected in an insoluble pool ( Figure 2d).…”

Section: Incorporation Into Rafts At the Tgn Is Not Required For Apicmentioning

confidence: 99%

Transcytotic Efflux from Early Endosomes Is Dependent on Cholesterol and Glycosphingolipids in Polarized Hepatic Cells

Nyasae

Hubbard

Tuma

2003

MBoC

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We examined the role that lipid rafts play in regulating apical protein trafficking in polarized hepatic cells. Rafts are postulated to form in the trans-Golgi network where they recruit newly synthesized apical residents and mediate their direct transport to the apical plasma membrane. In hepatocytes, single transmembrane and glycolipid-anchored apical proteins take the "indirect" route. They are transported from the trans-Golgi to the basolateral plasma membrane where they are endocytosed and transcytosed to the apical surface. Do rafts sort hepatic apical proteins along this circuitous pathway? We took two approaches to answer this question. First, we determined the detergent solubility of selected apical proteins and where in the biosynthetic pathway insolubility was acquired. Second, we used pharmacological agents to deplete raft components and assessed their effects on basolateral-to-apical transcytosis. We found that cholesterol and glycosphingolipids are required for delivery from basolateral early endosomes to the subapical compartment. In contrast, fluid phase uptake and clathrin-mediated internalization of recycling receptors were only mildly impaired. Apical protein solubility did not correlate with raft depletion or impaired transcytosis, suggesting other factors contribute to apical protein insolubility. Examination of apical proteins in Fao cells also revealed that raft-dependent sorting does not require the polarized cell context.

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Section: Incorporation Into Rafts At the Tgn Is Not Required For Apicmentioning

confidence: 99%

Transcytotic Efflux from Early Endosomes Is Dependent on Cholesterol and Glycosphingolipids in Polarized Hepatic Cells

Nyasae

Hubbard

Tuma

2003

MBoC

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“…For this purpose, HeLa cells were cotransfected with either VAP-B and a temperature sensitive mutant of vesicular stomatitis virus-glycoprotein (ts045 VSV-G) fused to YFP, or with Nir2, VAP-B, and YFP-VSV-G. At 40°C the VSV-G is synthesized and retained in the ER because of its misfolding (39). However, upon shifting the temperature to 32°C, the VSV-G protein folds and is transported to the Golgi apparatus and then to the cell surface within 20 -30 min and 60 -90 min, respectively.…”

Section: Coexpression Of Vap-b and Nir2mentioning

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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“…At 40°C, the tsO45VSV-G protein is retained in the ER because of a folding defect. Upon shifting to 32°C, the tsO45VSV-G protein folds correctly and exits ER in a synchronous wave as described previously (24). SYF, SYFsrc, and Srcϩ cells were transfected with a GFP-tsO45VSV-G protein-expressing plasmid and incubated at 40°C for 6 h to allow accumulation in the ER.…”

Section: Src Expression Reduces the Rate Of Golgi-to-er Traffic Of Thmentioning

confidence: 99%

Src Regulates Golgi Structure and KDEL Receptor-dependent Retrograde Transport to the Endoplasmic Reticulum

Bard

Mazelin

Péchoux-Longin

et al. 2003

Journal of Biological Chemistry

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The tyrosine kinase Src is present on the Golgi membranes. Its role, however, in the overall function and organization of the Golgi apparatus is unclear. We have found that in a cell line called SYF, which lacks the three ubiquitous Src-like kinases (Src, Yes, and Fyn), the organization of the Golgi apparatus is perturbed. The Golgi apparatus is composed of collapsed stacks and bloated cisternae in these cells. Expression of an activated form of Src relocated the KDEL receptor (KDEL-R) from the Golgi apparatus to the endoplasmic reticulum. Other Golgi-specific marker proteins were not affected under these conditions. Because of the specific effect of Src on the location of KDEL-R, we tested whether protein transport between ER and the Golgi apparatus involves Src. Transport of Pseudomonas exotoxin, which is transported to the ER by binding to the KDEL-R is accelerated by inhibition or genetic ablation of Src. Protein transport from ER to the Golgi apparatus however, is unaffected by Src deletion or inhibition. We propose that Src has an appreciable role in the organization of the Golgi apparatus, which may be linked to its involvement in protein transport from the Golgi apparatus to the endoplasmic reticulum.Src is activated by various cell surface receptors and phosphorylates numerous cellular proteins (for review, see Refs. 1 and 2). A significant fraction of Src is localized to the perinuclear region and the secretory vesicles in neuronal cells (3,4). It interacts with and phosphorylates proteins such as dynamin and synapsin (5-7) and synaptophysin (8) or cellugyrin (9), suggesting a role in the regulation of membrane traffic. Src and other Src family tyrosine kinases are also localized to the Golgi apparatus (3, 10). On the Golgi apparatus, Src interacts with the ubiquitin ligase Cbl, and Src activation leads to an increased recruitment of Cbl specifically at the Golgi. This indicates that Src-Cbl signaling might occur at this organelle (10). Further support for this proposal stems from recent findings that show that Src is involved in the activation of Ras on the Golgi apparatus following mitogenic stimulation (11). Src is also known to phosphorylate and interact with a Golgi apparatus-specific protein, Golgin 67 (12). However, the function of Src signaling at the Golgi remains unknown. The number of signaling molecules that associate with the Golgi membranes and regulate its function and organization is increasing and is known to include protein kinase D, which regulates Golgi-toplasma membrane trafficking (13) (14), and mitogen-activated protein kinase/extracellular signal-regulated kinase kinase (MEK) and polo-like kinase, which are essential for the fragmentation of the Golgi at the onset of mitosis (15) (16) (17). It is thus reasonable to propose that Src might also be involved in the structural and functional regulation of the Golgi membranes.A major issue in studies involving Src is the functional redundancy between the Src kinase family, which includes nine members (18). Knock-out studies have revea...

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Exit of newly synthesized membrane proteins from the trans cisterna of the Golgi complex to the plasma membrane.

Cited by 409 publications

References 41 publications

Transcytotic Efflux from Early Endosomes Is Dependent on Cholesterol and Glycosphingolipids in Polarized Hepatic Cells

Transcytotic Efflux from Early Endosomes Is Dependent on Cholesterol and Glycosphingolipids in Polarized Hepatic Cells

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

Src Regulates Golgi Structure and KDEL Receptor-dependent Retrograde Transport to the Endoplasmic Reticulum

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