scholarly journals Rab17 Regulates Membrane Trafficking through Apical Recycling Endosomes in Polarized Epithelial Cells

1998 ◽  
Vol 140 (5) ◽  
pp. 1039-1053 ◽  
Author(s):  
Paola Zacchi ◽  
Harald Stenmark ◽  
Robert G. Parton ◽  
Donata Orioli ◽  
Filip Lim ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Membrane Trafficking ◽  
Intracellular Transport ◽  
Cell Polarization ◽  
Small Gtpase ◽  
Recycling Endosome ◽  
Mutant Proteins ◽  
Confocal Immunofluorescence Microscopy ◽  
Polarized Epithelial Cells ◽  
And Function

A key feature of polarized epithelial cells is the ability to maintain the specific biochemical composition of the apical and basolateral plasma membrane domains while selectively allowing transport of proteins and lipids from one pole to the opposite by transcytosis. The small GTPase, rab17, a member of the rab family of regulators of intracellular transport, is specifically induced during cell polarization in the developing kidney. We here examined its intracellular distribution and function in both nonpolarized and polarized cells. By confocal immunofluorescence microscopy, rab17 colocalized with internalized transferrin in the perinuclear recycling endosome of BHK-21 cells. In polarized Eph4 cells, rab17 associated with the apical recycling endosome that has been implicated in recycling and transcytosis. The localization of rab17, therefore, strengthens the proposed homology between this compartment and the recycling endosome of nonpolarized cells. Basolateral to apical transport of two membrane-bound markers, the transferrin receptor and the FcLR 5-27 chimeric receptor, was specifically increased in Eph4 cells expressing rab17 mutants defective in either GTP binding or hydrolysis. Furthermore, the mutant proteins stimulated apical recycling of FcLR 5-27. These results support a role for rab17 in regulating traffic through the apical recycling endosome, suggesting a function in polarized sorting in epithelial cells.

scholarly journals The WD40 protein Morg1 facilitates Par6–aPKC binding to Crb3 for apical identity in epithelial cells

2013 ◽  
Vol 200 (5) ◽  
pp. 635-650 ◽  
Author(s):  
Junya Hayase ◽  
Sachiko Kamakura ◽  
Yuko Iwakiri ◽  
Yoshihiro Yamaguchi ◽  
Tomoko Izaki ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Epithelial Cells ◽  
Tight Junction ◽  
Apical Membrane ◽  
Transmembrane Protein ◽  
Cyst Formation ◽  
Cell Polarization ◽  
Small Gtpase ◽  
Apical Surface ◽  
And Function

Formation of apico-basal polarity in epithelial cells is crucial for both morphogenesis (e.g., cyst formation) and function (e.g., tight junction development). Atypical protein kinase C (aPKC), complexed with Par6, is considered to translocate to the apical membrane and function in epithelial cell polarization. However, the mechanism for translocation of the Par6–aPKC complex has remained largely unknown. Here, we show that the WD40 protein Morg1 (mitogen-activated protein kinase organizer 1) directly binds to Par6 and thus facilitates apical targeting of Par6–aPKC in Madin-Darby canine kidney epithelial cells. Morg1 also interacts with the apical transmembrane protein Crumbs3 to promote Par6–aPKC binding to Crumbs3, which is reinforced with the apically localized small GTPase Cdc42. Depletion of Morg1 disrupted both tight junction development in monolayer culture and cyst formation in three-dimensional culture; apico-basal polarity was notably restored by forced targeting of aPKC to the apical surface. Thus, Par6–aPKC recruitment to the premature apical membrane appears to be required for definition of apical identity of epithelial cells.

scholarly journals Interactions of Lipid Droplets with the Intracellular Transport Machinery

2021 ◽  
Vol 22 (5) ◽  
pp. 2776
Author(s):  
Selma Yilmaz Dejgaard ◽  
John F. Presley
Keyword(s):  
Membrane Trafficking ◽  
Lipid Droplets ◽  
Intracellular Transport ◽  
Neutral Lipids ◽  
Small Gtpases ◽  
Lipid Phase ◽  
Intracellular Organelles ◽  
And Function ◽  
Lipid Phase Separation ◽  
Endocytic Pathways

Historically, studies of intracellular membrane trafficking have focused on the secretory and endocytic pathways and their major organelles. However, these pathways are also directly implicated in the biogenesis and function of other important intracellular organelles, the best studied of which are peroxisomes and lipid droplets. There is a large recent body of work on these organelles, which have resulted in the introduction of new paradigms regarding the roles of membrane trafficking organelles. In this review, we discuss the roles of membrane trafficking in the life cycle of lipid droplets. This includes the complementary roles of lipid phase separation and proteins in the biogenesis of lipid droplets from endoplasmic reticulum (ER) membranes, and the attachment of mature lipid droplets to membranes by lipidic bridges and by more conventional protein tethers. We also discuss the catabolism of neutral lipids, which in part results from the interaction of lipid droplets with cytosolic molecules, but with important roles for both macroautophagy and microautophagy. Finally, we address their eventual demise, which involves interactions with the autophagocytotic machinery. We pay particular attention to the roles of small GTPases, particularly Rab18, in these processes.

scholarly journals Clustering in the Golgi apparatus governs sorting and function of GPI‐APs in polarized epithelial cells

FEBS Letters ◽  
2019 ◽  
Vol 593 (17) ◽  
pp. 2351-2365 ◽  
Author(s):  
Stéphanie Lebreton ◽  
Simona Paladino ◽  
Chiara Zurzolo
Keyword(s):  
Epithelial Cells ◽  
Golgi Apparatus ◽  
Polarized Epithelial Cells ◽  
And Function

scholarly journals Mumps Virus Is Released from the Apical Surface of Polarized Epithelial Cells, and the Release Is Facilitated by a Rab11-Mediated Transport System

2015 ◽  
Vol 89 (23) ◽  
pp. 12026-12034 ◽  
Author(s):  
Hiroshi Katoh ◽  
Yuichiro Nakatsu ◽  
Toru Kubota ◽  
Masafumi Sakata ◽  
Makoto Takeda ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Measles Virus ◽  
Intracellular Transport ◽  
Systemic Infection ◽  
Mumps Virus ◽  
Progeny Virus ◽  
Apical Surface ◽  
Virus Release ◽  
Polarized Cells ◽  
Polarized Epithelial Cells

ABSTRACTMumps virus (MuV) is an airborne virus that causes a systemic infection in patients.In vivo, the epithelium is a major replication site of MuV, and thus, the mode of MuV infection of epithelial cells is a subject of interest. Our data in the present study showed that MuV entered polarized epithelial cells via both the apical and basolateral surfaces, while progeny viruses were predominantly released from the apical surface. In polarized cells, intracellular transport of viral ribonucleoprotein (vRNP) complexes was dependent on Rab11-positive endosomes, and vRNP complexes were transported to the apical membrane. Expression of a dominant negative form of Rab11 (Rab11S25N) reduced the progeny virus release in polarized cells but not in nonpolarized cells. Although in this way these effects were correlated with cell polarity, Rab11S25N did not modulate the direction of virus release from the apical surface. Therefore, our data suggested that Rab11 is not a regulator of selective apical release of MuV, although it acts as an activator of virus release from polarized epithelial cells. In addition, our data and previous studies on Sendai virus, respiratory syncytial virus, and measles virus suggested that selective apical release from epithelial cells is used by many paramyxoviruses, even though they cause either a systemic infection or a local respiratory infection.IMPORTANCEMumps virus (MuV) is the etiological agent of mumps and causes a systemic infection. However, the precise mechanism by which MuV breaks through the epithelial barriers and achieves a systemic infection remains unclear. In the present study, we show that the entry of MuV is bipolar, while the release is predominantly from the apical surface in polarized epithelial cells. In addition, the release of progeny virus was facilitated by a Rab11-positive recycling endosome and microtubule network. Our data provide important insights into the mechanism of transmission and pathogenesis of MuV.

The role of regulated CFTR trafficking in epithelial secretion

2003 ◽  
Vol 285 (1) ◽  
pp. C1-C18 ◽  
Author(s):  
Carol A. Bertrand ◽  
Raymond A. Frizzell
Keyword(s):  
Epithelial Cells ◽  
Membrane Trafficking ◽  
Cellular Localization ◽  
Secretory Pathway ◽  
Molecular Mechanisms ◽  
Experimental Manipulation ◽  
Experimental Conditions ◽  
Functional Studies ◽  
Cellular Context ◽  
Polarized Epithelial Cells

The focus of this review is the regulated trafficking of the cystic fibrosis transmembrane conductance regulator (CFTR) in distal compartments of the protein secretory pathway and the question of how changes in CFTR cellular distribution may impact on the functions of polarized epithelial cells. We summarize data concerning the cellular localization and activity of CFTR and attempt to synthesize often conflicting results from functional studies of regulated endocytosis and exocytosis in CFTR-expressing cells. In some instances, findings that are inconsistent with regulated CFTR trafficking may result from the use of overexpression systems or nonphysiological experimental conditions. Nevertheless, judging from data on other transporters, an appropriate cellular context is necessary to support regulated CFTR trafficking, even in epithelial cells. The discovery that disease mutations can influence CFTR trafficking in distal secretory and recycling compartments provides support for the concept that regulated CFTR recycling contributes to normal epithelial function, including the control of apical CFTR channel density and epithelial protein secretion. Finally, we propose molecular mechanisms for regulated CFTR endocytosis and exocytosis that are based on CFTR interactions with other proteins, particularly those whose primary function is membrane trafficking. These models provide testable hypotheses that may lead to elucidation of CFTR trafficking mechanisms and permit their experimental manipulation in polarized epithelial cells.

The role of lipid rafts in signalling and membrane trafficking in T lymphocytes

2001 ◽  
Vol 114 (22) ◽  
pp. 3957-3965
Author(s):  
Miguel A. Alonso ◽  
Jaime Millán
Keyword(s):  
T Lymphocytes ◽  
Epithelial Cells ◽  
Lipid Rafts ◽  
T Cell Activation ◽  
Membrane Trafficking ◽  
Intracellular Transport ◽  
Cell Activation ◽  
Membrane Microdomains ◽  
Caveolin 1 ◽  
Lipid Species

Combinatorial association of different lipid species generates microheterogeneity in biological membranes. The association of glycosphingolipids with cholesterol forms membrane microdomains – lipid rafts – that are involved in specialised pathways of protein/lipid transport and signalling. Lipid rafts are normally dispersed in cellular membranes and appear to require specialised machinery to reorganise them to operate. Caveolin-1 and MAL are members of two different protein families involved in reorganisation of lipid rafts for signalling and/or intracellular transport in epithelial cells. T cell activation induces a rapid compartmentalisation of signalling machinery into reorganised rafts that are used as platforms for the assembly of the signalling complex. Costimulatory molecules participate in this process by providing signals that mobilise raft lipids and proteins, and remodel the cytoskeleton to the contact site. As in epithelial cells, rafts are used also as vesicular carriers for membrane trafficking in T lymphocytes. Furthermore, there are potential similarities between the specialised protein machinery underlying raft-mediated processes in T lymphocytes and polarised epithelial cells.

scholarly journals Rab11 regulates recycling through the pericentriolar recycling endosome.

1996 ◽  
Vol 135 (4) ◽  
pp. 913-924 ◽  
Author(s):  
O Ullrich ◽  
S Reinsch ◽  
S Urbé ◽  
M Zerial ◽  
R G Parton
Keyword(s):  
Immunofluorescence Microscopy ◽  
Bound State ◽  
Small Gtpases ◽  
Recycling Endosome ◽  
Functional Studies ◽  
Confocal Immunofluorescence Microscopy ◽  
Confocal Immunofluorescence ◽  
Recycling Pathway ◽  
And Function ◽  
Perinuclear Area

Small GTPases of the rab family are crucial elements of the machinery that controls membrane traffic. In the present study, we examined the distribution and function of rab11. Rab11 was shown by confocal immunofluorescence microscopy and EM to colocalize with internalized transferrin in the pericentriolar recycling compartment of CHO and BHK cells. Expression of rab11 mutants that are preferentially in the GTP- or GDP-bound state caused opposite effects on the distribution of transferrin-containing elements; rab11-GTP expression caused accumulation of labeled elements in the perinuclear area of the cell, whereas rab11-GDP caused a dispersion of the transferrin labeling. Functional studies showed that the early steps of uptake and recycling for transferrin were not affected by overexpression of rab11 proteins. However, recycling from the later recycling endosome was inhibited in cells overexpressing the rab11-GDP mutant. Rab5, which regulates early endocytic trafficking, acted before rab11 in the transferrin-recycling pathway as expression of rab5-GTP prevented transport to the rab11-positive recycling endosome. These results suggest a novel role for rab11 in controlling traffic through the recycling endosome.

Composition and function of PDZ protein complexes during cell polarization

2003 ◽  
Vol 285 (3) ◽  
pp. F377-F387 ◽  
Author(s):  
Michael H. Roh ◽  
Ben Margolis
Keyword(s):  
Epithelial Cells ◽  
Current Knowledge ◽  
Protein Complexes ◽  
Cell Types ◽  
Cell Polarization ◽  
Differential Distribution ◽  
Pdz Proteins ◽  
Homologous Protein ◽  
Pdz Protein ◽  
And Function

Complexes consisting of PDZ proteins have been implicated in a variety of cellular processes. In recent years, it has become increasingly clear that PDZ proteins play essential roles during the establishment of spatial asymmetry in various metazoan cell types such as epithelial cells. Epithelial cells possess asymmetry with respect to the apicobasal axis reflected by the differential distribution of proteins and lipids in the apical and basolateral surfaces. In Drosophila, three PDZ protein complexes have been shown to play crucial functions during the establishment of cell-cell adhesions and epithelial cell polarity: Bazooka/Dm-Par6/DaPKC, Crumbs/Stardust/Discs Lost, and Scribble/Discs Large/Lethal Giant Larvae. In this review, we focus primarily on our current knowledge of the localization and function of these complexes in Drosophila epithelia. We also discuss recent data that enhance our understanding of the homologous protein complexes and their roles during junctional assembly and polarization of mammalian epithelial cells.

scholarly journals A small rab GTPase is distributed in cytoplasmic vesicles in non polarized cells but colocalizes with the tight junction marker ZO-1 in polarized epithelial cells

1994 ◽  
Vol 124 (1) ◽  
pp. 101-115 ◽  
Author(s):  
A Zahraoui ◽  
G Joberty ◽  
M Arpin ◽  
JJ Fontaine ◽  
R Hellio ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Tight Junction ◽  
Tight Junctions ◽  
Small Gtpase ◽  
Junctional Complex ◽  
Rab Gtpase ◽  
Cytoplasmic Vesicles ◽  
Microscopy Analysis ◽  
Polarized Epithelial Cells ◽  
Kidney Liver

Small rab/Ypt1/Sec4 GTPase family have been involved in the regulation of membrane traffic along the biosynthetic and endocytic pathways in eucaryotic cells. Polarized epithelial cells have morphologically and functionally distinct apical and basolateral surfaces separated by tight junctions. The establishment and maintenance of these structures require delivery of membrane proteins and lipids to these domains. In this work, we have isolated a cDNA clone from a human intestinal cDNA library encoding a small GTPase, rab13, closely related to the yeast Sec4 protein. Confocal microscopy analysis on polarized Caco-2 cells shows that rab13 protein colocalized with the tight junction marker ZO-1. Cryostat sections of tissues confirm that rab13 localized to the junctional complex region of a variety of epithelia, including intestine, kidney, liver, and of endothelial cells. This localization requires assembly and integrity of the tight junctions. Disruption of tight junctions by incubation in low Ca2+ media induces the redistribution of rab13. In cells devoid of tight junctions, rab13 was found associated with vesicles dispersed throughout the cytoplasm. Cell-cell contacts initiated by E-cadherin in transfected L cells do not recruit rab13 to the resulting adherens-like junction complexes. The participation of rab13 in polarized transport, in the assembly and/or the activity of tight junctions is discussed.

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