Membrane and secretory proteins are transported from the Golgi complex to the sinusoidal plasmalemma of hepatocytes by distinct vesicular carriers.

Saucan, Lucian; Palade, George E.

doi:10.1083/jcb.125.4.733

Cited by 89 publications

(80 citation statements)

References 28 publications

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“…In the trans-Golgi network (TGN), the newly synthesized proteins are terminally glycosylated by the addition of N-acetylglucosamine, galactose, sialic acid and/or fucose moieties. While the mechanistic details regulating sorting at the TGN are not fully understood, secreted proteins are packaged into discrete vesicles, delivered to the basolateral surface and released [75]. In general, surface delivery of secretory proteins is a microtubule-dependent process that is mediated by a host of other molecules [20,53,69,72].…”

Section: Ethanol-induced Impairment Of Constitutive Secretionmentioning

confidence: 99%

Alcohol consumption impairs hepatic protein trafficking: mechanisms and consequences

2009

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Alcoholic liver disease is a major biomedical health concern in the United States. Despite considerable research efforts aimed at understanding the progression of the disease, the specific mechanisms leading to alcohol-induced damage remain elusive. Numerous proteins are known to have alcohol-induced alterations in their dynamics. Defining these defects in protein trafficking is an active area of research. In general, two trafficking pathways are affected: transport of newly synthesized secretory or membrane glycoproteins from the Golgi to the basolateral membrane and clathrin-mediated endocytosis from the sinusoidal surface. Both impaired secretion and internalization require ethanol metabolism and are likely mediated by acetaldehyde. Although the mechanisms by which ethanol exposure impairs protein trafficking are not fully understood, recent work implicates alcohol-induced modifications on tubulin or components of the clathrin machinery as potential mediators. Furthermore, the physiological ramifications of impaired protein trafficking are not fully understood. In this review, we will list and discuss the proteins whose trafficking patterns are known to be impaired by ethanol exposure. We will then describe what is known about the possible mechanisms leading to impaired protein trafficking and how disrupted protein trafficking alters liver function and may explain clinical features of the alcoholic patient.

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Section: Ethanol-induced Impairment Of Constitutive Secretionmentioning

confidence: 99%

Alcohol consumption impairs hepatic protein trafficking: mechanisms and consequences

2009

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“…Preparation of Rat Liver Fractions-Fractions were prepared from rat liver by density gradient centrifugation and characterized as described previously (37,38). The protein concentration of each fraction was determined by BCA assay (Pierce), and 40 g of protein of each fraction was solubilized in Laemmli sample buffer and separated by SDS-PAGE.…”

Section: Methodsmentioning

confidence: 99%

“…9) and was not detected under these conditions in the Golgi light, Golgi heavy, and CV1 fractions. CV1 and CV2 fractions typically contain a mixture of ER-Golgi transport vesicles, TGN (trans Golgi network)-derived vesicles, transcytotic vesicles, and vesicles derived from early and late endosomes (37,38). Thus the biochemical evidence together with the localization results support the conclusion that GIV is associated with COPI, ER-Golgi transport vesicles.…”

Section: Giv Is Concentrated In Carrier Vesicle (Cv2)-enriched Fractimentioning

confidence: 99%

“…Liver-To obtain biochemical evidence on the localization of GIV we determined the distribution of GIV in fractions prepared from rat liver in which carrier vesicles can be separated from Golgi and other membranes by sucrose gradient centrifugation (37,38). Golgi light, Golgi heavy, CV1 and CV2, and residual membrane fractions were immunoblotted for GIV along with ␤-COP, G␣ i1 , G␣ i1/2 , G␣ i3 , and G␣ s .…”

Section: Giv Is Concentrated In Carrier Vesicle (Cv2)-enriched Fractimentioning

confidence: 99%

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Identification and Characterization of GIV, a Novel Gαi/s -interacting Protein Found on COPI, Endoplasmic Reticulum-Golgi Transport Vesicles

Le-Niculescu

Niesman

Fischer

et al. 2005

Journal of Biological Chemistry

142

167

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In this report, we characterize GIV (G␣-interacting vesicle-associated protein), a novel protein that binds members of the G␣ i and G␣ s subfamilies of heterotrimeric G proteins. The G␣ interaction site was mapped to an 83-amino acid region of GIV that is enriched in highly charged amino acids. BLAST searches revealed two additional mammalian family members, Daple and an uncharacterized protein, FLJ00354. These family members share the highest homology at the G␣ binding domain, are homologous at the N terminus and central coiled coil domain but diverge at the C terminus. Using affinitypurified IgG made against two different regions of the protein, we localized GIV to COPI, endoplasmic reticulum (ER)-Golgi transport vesicles concentrated in the Golgi region in GH3 pituitary cells and COS7 cells. Identification as COPI vesicles was based on colocalization with ␤-COP, a marker for these vesicles. GIV also codistributes in the Golgi region with endogenous calnuc and the KDEL receptor, which are cis Golgi markers and with G␣ i3 -yellow fluorescent protein expressed in COS7 cells. By immunoelectron microscopy, GIV colocalizes with ␤-COP and G␣ i3 on vesicles found in close proximity to ER exit sites and to cis Golgi cisternae. In cell fractions prepared from rat liver, GIV is concentrated in a carrier vesicle fraction (CV2) enriched in ER-Golgi transport vesicles. ␤-COP and several G␣ subunits (G␣ i1-3 , G␣ s ) are also most enriched in CV2. Our results demonstrate the existence of a novel G␣-interacting protein associated with COPI transport vesicles that may play a role in G␣-mediated effects on vesicle trafficking within the Golgi and/or between the ER and the Golgi.

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“…Furthermore, some of these transport steps may actually involve two parallel pathways. For instance, TGN to basolateral plasma membrane delivery in both Madin-Darby canine kidney (MDCK) cells and rat hepatocytes seems to use separate vesicles for transporting membrane proteins or secretory proteins (Boll et al, 1991;Saucan and Palade, 1994). Recent studies by Ikonen et al, 1995 have demonstrated that the fusion of biosynthetic vesicles (carrying the vesicular stomatitis virus G protein as a marker protein) with the basolateral surface required NSF, aSNAP, and VAMP/synaptobrevin (Ikonen et al, 1995;Wilson, 1995).…”

Section: Introductionmentioning

confidence: 99%

Differential localization of syntaxin isoforms in polarized Madin-Darby canine kidney cells.

Low

Chapin

Weimbs

et al. 1996

MBoC

224

223

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Syntaxins, integral membrane proteins that are part of the ubiquitous membrane fusion machinery, are thought to act as target membrane receptors during the process of vesicle docking and fusion. Several isoforms of the syntaxin family have been previously identified in mammalian cells, some of which are localized to the plasma membrane. We investigated the subcellular localization of these putative plasma membrane syntaxins in polarized epithelial cells, which are characterized by the presence of distinct apical and basolateral plasma membrane domains. Syntaxins 2, 3, and 4 were found to be endogenously present in Madin-Darby canine kidney cells. The localization of syntaxins 1A, 1B, 2, 3, and 4 in stably transfected Madin-Darby canine kidney cell lines was studied with confocal immunofluorescence microscopy. Each syntaxin isoform was found to have a unique pattern of localization. Syntaxins 1A and 1B were present only in intracellular structures, with little or no apparent plasma membrane staining. In contrast, syntaxin 2 was found on both the apical and basolateral surface, whereas the plasma membrane localization of syntaxins 3 and 4 were restricted to the apical or basolateral domains, respectively. Syntaxins are therefore the first known components of the plasma membrane fusion machinery that are differentially localized in polarized cells, suggesting that they may play a central role in targeting specificity.

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Membrane and secretory proteins are transported from the Golgi complex to the sinusoidal plasmalemma of hepatocytes by distinct vesicular carriers.

Cited by 89 publications

References 28 publications

Alcohol consumption impairs hepatic protein trafficking: mechanisms and consequences

Alcohol consumption impairs hepatic protein trafficking: mechanisms and consequences

Identification and Characterization of GIV, a Novel Gαi/s -interacting Protein Found on COPI, Endoplasmic Reticulum-Golgi Transport Vesicles

Differential localization of syntaxin isoforms in polarized Madin-Darby canine kidney cells.

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