scholarly journals Sorting Competition with Membrane-permeable Peptides in Intact Epithelial Cells Revealed Discrimination of Transmembrane Proteins Not Only at thetrans-Golgi Network but Also at Pre-Golgi Stages

2004 ◽  
Vol 279 (17) ◽  
pp. 17376-17383 ◽  
Author(s):  
Andrea Soza ◽  
Andrés Norambuena ◽  
Jorge Cancino ◽  
Erwin de la Fuente ◽  
Peter Henklein ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Transmembrane Proteins ◽  
Golgi Network

scholarly journals Adaptor proteins involved in polarized sorting

2014 ◽  
Vol 204 (1) ◽  
pp. 7-17 ◽  
Author(s):  
Juan S. Bonifacino
Keyword(s):  
Epithelial Cells ◽  
Transmembrane Proteins ◽  
Adaptor Protein ◽  
Adaptor Proteins ◽  
Coat Proteins ◽  
Membrane Domains ◽  
Recycling Endosomes ◽  
Polarized Cells ◽  
Cytosolic Domains ◽  
Golgi Network

Polarized cells such as epithelial cells and neurons exhibit different plasma membrane domains with distinct protein compositions. Recent studies have shown that sorting of transmembrane proteins to the basolateral domain of epithelial cells and the somatodendritic domain of neurons is mediated by recognition of signals in the cytosolic domains of the proteins by adaptors. These adaptors are components of protein coats associated with the trans-Golgi network and/or recycling endosomes. The clathrin-associated adaptor protein 1 (AP-1) complex plays a preeminent role in this process, although other adaptors and coat proteins, such as AP-4, ARH, Numb, exomer, and retromer, have also been implicated.

scholarly journals Putative linear motifs mediate the trafficking to apical and basolateral membranes

2020 ◽  
Author(s):  
Laszlo Dobson ◽  
András Zeke ◽  
Levente Szekeres ◽  
Tamás Langó ◽  
Gábor Tusnády
Keyword(s):  
Epithelial Cells ◽  
Drug Transport ◽  
Basolateral Membrane ◽  
Transmembrane Proteins ◽  
Transport Processes ◽  
Membrane Domains ◽  
Protein Distribution ◽  
Basolateral Membranes ◽  
Linear Motifs ◽  
Cellular Components

AbstractCell polarity refers to the asymmetric organisation of cellular components in various cells. Epithelial cells are the best known examples of polarized cells, featuring apical and basolateral membrane domains. Despite huge efforts, the exact rules governing the protein distribution in such domains are still elusive. In this study we examined linear motifs accumulating in these parts and based on the results we prepared ‘Classical’ and Convolutional Neural Networks to classify human transmembrane proteins localizing into apical/basolateral membranes. Asymmetric expression of drug transporters results in vectorial drug transport, governing the pharmacokinetics of numerous substances, yet the data on how proteins are sorted in epithelial cells is very scattered. The provided dataset may offer help to experimentalists to characterize novel molecular targets to regulate transport processes more precisely.

scholarly journals Herpes Simplex Virus Entry by a Nonconventional Endocytic Pathway

2020 ◽  
Vol 94 (24) ◽  
Author(s):  
Giulia Tebaldi ◽  
Suzanne M. Pritchard ◽  
Anthony V. Nicola
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Epithelial Cells ◽  
Retrograde Transport ◽  
Endocytic Pathway ◽  
Host Cells ◽  
Herpes Simplex Virus 1 ◽  
Simplex Virus ◽  
Golgi Network ◽  
Hsv 1

ABSTRACT Herpes simplex virus 1 (HSV-1) causes significant morbidity and mortality in humans worldwide. HSV-1 enters epithelial cells via an endocytosis mechanism that is low-pH dependent. However, the precise intracellular pathway has not been identified, including the compartment where fusion occurs. In this study, we utilized a combination of molecular and pharmacological approaches to better characterize HSV entry by endocytosis. HSV-1 entry was unaltered in both cells treated with small interfering RNA (siRNA) to Rab5 or Rab7 and cells expressing dominant negative forms of these GTPases, suggesting entry is independent of the conventional endo-lysosomal network. The fungal metabolite brefeldin A (BFA) and the quinoline compound Golgicide A (GCA) inhibited HSV-1 entry via beta-galactosidase reporter assay and impaired incoming virus transport to the nuclear periphery, suggesting a role for trans-Golgi network (TGN) functions and retrograde transport in HSV entry. Silencing of Rab9 or Rab11 GTPases, which are involved in the retrograde transport pathway, resulted in only a slight reduction in HSV infection. Together, these results suggest that HSV enters host cells by an intracellular route independent of the lysosome-terminal endocytic pathway. IMPORTANCE Herpes simplex virus 1 (HSV-1), the prototype alphaherpesvirus, is ubiquitous in the human population and causes lifelong infection that can be fatal in neonatal and immunocompromised individuals. HSV enters many cell types by endocytosis, including epithelial cells, the site of primary infection in the host. The intracellular itinerary for HSV entry remains unclear. We probed the potential involvement of several Rab GTPases in HSV-1 entry and suggest that endocytic entry of HSV-1 is independent of the canonical lysosome-terminal pathway. A nontraditional endocytic route may be employed, such as one that intersects with the trans-Golgi network (TGN). These results may lead to novel targets for intervention.

scholarly journals Exocytosis from permeabilized lactating mouse mammary epithelial cells. Stimulation by Ca2+ and phorbol ester, but inhibition of regulated exocytosis by guanosine 5′-[γ-thio]triphosphate

1992 ◽  
Vol 286 (1) ◽  
pp. 13-15 ◽  
Author(s):  
M D Turner ◽  
C J Wilde ◽  
R D Burgoyne
Keyword(s):  
Epithelial Cells ◽  
Protein Secretion ◽  
Phorbol Ester ◽  
Mammary Epithelial Cells ◽  
Post Partum ◽  
Mammary Epithelial ◽  
Independent Manner ◽  
Permeabilized Cells ◽  
A Site ◽  
Golgi Network

Lactating mouse mammary epithelial cells secrete large amounts of milk protein via constitutive or regulated exocytotic pathways. Secretion through both pathways was quantified by assaying the release of [35S]methionine-labelled trichloroacetic acid-precipitable proteins from digitonin-permeabilized secretory acini isolated from mammary glands of 10-day-post-partum lactating mice. Protein secretion from the isolated permeabilized cells was either Ca(2+)-dependent (regulated) or Ca(2+)-independent (constitutive). In both cases there was a requirement for ATP. Addition of the phorbol ester phorbol 12-myristate 13-acetate (PMA) caused a marked increase in the percentage protein secretion from the cells in a Ca(2+)-independent manner. However, the non-hydrolysable GTP analogue guanosine 5′-[gamma-thio]triphosphate (GTP[S]) caused a partial inhibition of Ca(2+)-dependent exocytosis, while having no significant effect on Ca(2+)-independent exocytosis. Thus the GTP[S] is exerting its effect on the regulated pathway at a site subsequent to protein sorting and packaging into secretory vesicles at the trans-Golgi network.

Polarization-dependent apical membrane CFTR targeting underlies cAMP-stimulated Cl- secretion in epithelial cells

1994 ◽  
Vol 266 (1) ◽  
pp. C254-C268 ◽  
Author(s):  
A. P. Morris ◽  
S. A. Cunningham ◽  
A. Tousson ◽  
D. J. Benos ◽  
R. A. Frizzell
Keyword(s):  
Epithelial Cells ◽  
Apical Membrane ◽  
Brefeldin A ◽  
Microtubule Organizing Center ◽  
Cl Secretion ◽  
Organizing Center ◽  
Reversible Time ◽  
Golgi Network ◽  
Ht 29 ◽  
Cl Conductance

The relationship between adenosine 3',5'-cyclic monophosphate (cAMP)-mediated Cl- secretion and the cellular location of the cystic fibrosis transmembrane conductance regulator (CFTR) was determined in both polarized (Cl.19A) and unpolarized (parental) HT-29 colonocytes expressing similar levels of CFTR mRNA and protein. CFTR immunolocalized to the apical membrane domain of polarized colonocytes exhibiting cAMP-responsive Cl- secretion. In contrast, CFTR staining was perinuclear in unpolarized colonocytes, which gave little or no cAMP-stimulated Cl- conductance responses. Thus cAMP-stimulated Cl- secretion coincided with an apical localization of CFTR. Brefeldin A (BFA) was used to perturb glycoprotein targeting in these cells. In polarized colonocytes, BFA caused a reversible, time-dependent decrease in the Cl-conductance response to cAMP but not Ca2+. Apical CFTR redistributed into large coalesced intracellular vesicles, located within the same plane as the microtubule organizing center, a marker for the trans-Golgi network (TGN). In preconfluent monolayers or unpolarized HT-29 cells, BFA had no effect on CFTR staining, which remained perinuclear. Mature, Golgi-processed CFTR protein was isolated from both polarized and unpolarized colonocytes. Thus the mechanism for polarization-dependent apical membrane CFTR targeting and the acquisition of cAMP-dependent Cl- secretion lies at or beyond the late Golgi-TGN in epithelial cells.

scholarly journals Sphingomyelin homeostasis is required to form functional enzymatic domains at the trans-Golgi network

2014 ◽  
Vol 206 (5) ◽  
pp. 609-618 ◽  
Author(s):  
Josse van Galen ◽  
Felix Campelo ◽  
Emma Martínez-Alonso ◽  
Margherita Scarpa ◽  
José Ángel Martínez-Menárguez ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Hela Cells ◽  
Transmembrane Proteins ◽  
Short Chain ◽  
Membrane Domains ◽  
Trans Golgi Network ◽  
And Function ◽  
Golgi Network ◽  
Specific Membrane

Do lipids such as sphingomyelin (SM) that are known to assemble into specific membrane domains play a role in the organization and function of transmembrane proteins? In this paper, we show that disruption of SM homeostasis at the trans-Golgi network (TGN) by treatment of HeLa cells with d-ceramide-C6, which was converted together with phosphatidylcholine to short-chain SM and diacylglycerol by SM synthase, led to the segregation of Golgi-resident proteins from each other. We found that TGN46, which cycles between the TGN and the plasma membrane, was not sialylated by a sialyltransferase at the TGN and that this enzyme and its substrate TGN46 could not physically interact with each other. Our results suggest that SM organizes transmembrane proteins into functional enzymatic domains at the TGN.

scholarly journals Regulation of Membrane Trafficking by a Novel Cdc42-related Protein in Caenorhabditis elegans Epithelial Cells

2005 ◽  
Vol 16 (4) ◽  
pp. 1629-1639 ◽  
Author(s):  
S. Jenna ◽  
M.-E. Caruso ◽  
A. Emadali ◽  
D. T. Nguyên ◽  
M. Dominguez ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Epithelial Cells ◽  
Membrane Trafficking ◽  
Rho Gtpases ◽  
Related Protein ◽  
Recycling Endosomes ◽  
C Elegans ◽  
Apical Trafficking ◽  
Golgi Network

Rho GTPases are mainly known for their implication in cytoskeleton remodeling. They have also been recently shown to regulate various aspects of membrane trafficking. Here, we report the identification and the characterization of a novel Caenorhabditis elegans Cdc42-related protein, CRP-1, that shows atypical enzymatic characteristics in vitro. Expression in mouse fibroblasts revealed that, in contrast with CDC-42, CRP-1 was unable to reorganize the actin cytoskeleton and mainly localized to trans-Golgi network and recycling endosomes. This subcellular localization, as well as its expression profile restricted to a subset of epithelial-like cells in C. elegans, suggested a potential function for this protein in polarized membrane trafficking. Consistent with this hypothesis, alteration of CRP-1 expression affected the apical trafficking of CHE-14 in vulval and rectal epithelial cells and sphingolipids (C6-NBD-ceramide) uptake and/or trafficking in intestinal cells. However, it did not affect basolateral trafficking of myotactin in the pharynx and the targeting of IFB-2 and AJM-1, two cytosolic apical markers of intestine epithelial cells. Hence, our data demonstrate a function for CRP-1 in the regulation of membrane trafficking in a subset of cells with epithelial characteristics.

Cigarette Smoking Condensate Disrupts Endoplasmic Reticulum–Golgi Network Homeostasis Through GOLPH3 Expression in Normal Lung Epithelial Cells

2016 ◽  
Vol 18 (9) ◽  
pp. 1877-1885 ◽  
Author(s):  
Kyeong-Nam Yu ◽  
Hyeon-Jeong Kim ◽  
Sanghwa Kim ◽  
Orkhouselenge Dawaadamdin ◽  
Ah-Young Lee ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Epithelial Cells ◽  
Cigarette Smoking ◽  
Lung Epithelial Cells ◽  
Normal Lung ◽  
Lung Epithelial ◽  
Golgi Network
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