Basolateral Sorting of Human Poliovirus Receptor α Involves an Interaction with the μ1B Subunit of the Clathrin Adaptor Complex in Polarized Epithelial Cells

2001 ◽  
Vol 287 (4) ◽  
pp. 941-948 ◽  
Author(s):  
Seii Ohka ◽  
Hiroshi Ohno ◽  
Koujiro Tohyama ◽  
Akio Nomoto
Keyword(s):  
Epithelial Cells ◽  
Poliovirus Receptor ◽  
Polarized Epithelial Cells ◽  
Clathrin Adaptor

scholarly journals Arf6 regulates AP-1B–dependent sorting in polarized epithelial cells

2011 ◽  
Vol 194 (6) ◽  
pp. 873-887 ◽  
Author(s):  
Elina Shteyn ◽  
Lucy Pigati ◽  
Heike Fölsch
Keyword(s):  
Epithelial Cells ◽  
Dominant Negative ◽  
Recycling Endosomes ◽  
Membrane Recruitment ◽  
Important Regulator ◽  
Basolateral Plasma Membrane ◽  
Polarized Epithelial Cells ◽  
Clathrin Adaptor ◽  
Basolateral Targeting

The epithelial cell–specific clathrin adaptor complex AP-1B facilitates the sorting of various transmembrane proteins from recycling endosomes (REs) to the basolateral plasma membrane. Despite AP-1B’s clear importance in polarized epithelial cells, we still do not fully understand how AP-1B orchestrates basolateral targeting. Here we identify the ADP-ribosylation factor 6 (Arf6) as an important regulator of AP-1B. We show that activated Arf6 pulled down AP-1B in vitro. Furthermore, interfering with Arf6 function through overexpression of dominant-active Arf6Q67L or dominant-negative Arf6D125N, as well as depletion of Arf6 with short hairpin RNA (shRNA), led to apical missorting of AP-1B–dependent cargos. In agreement with these data, we found that Arf6 colocalized with AP-1B and transferrin receptor (TfnR) in REs. In addition, we observed specific recruitment of AP-1B into Arf6-induced membrane ruffles in nonpolarized cells. We conclude that activated Arf6 directs membrane recruitment of AP-1B, thus regulating AP-1B’s functions in polarized epithelial cells.

scholarly journals Phosphatidylinositol 3,4,5-trisphosphate Localization in Recycling Endosomes Is Necessary for AP-1B–dependent Sorting in Polarized Epithelial Cells

2010 ◽  
Vol 21 (1) ◽  
pp. 95-105 ◽  
Author(s):  
Ian C. Fields ◽  
Shelby M. King ◽  
Elina Shteyn ◽  
Richard S. Kang ◽  
Heike Fölsch
Keyword(s):  
Plasma Membrane ◽  
Epithelial Cell ◽  
Epithelial Cells ◽  
Basolateral Membrane ◽  
Apical Plasma Membrane ◽  
Amino Acid Residues ◽  
Recycling Endosomes ◽  
C Terminus ◽  
Polarized Epithelial Cells ◽  
Clathrin Adaptor

Polarized epithelial cells coexpress two almost identical AP-1 clathrin adaptor complexes: the ubiquitously expressed AP-1A and the epithelial cell–specific AP-1B. The only difference between the two complexes is the incorporation of the respective medium subunits μ1A or μ1B, which are responsible for the different functions of AP-1A and AP-1B in TGN to endosome or endosome to basolateral membrane targeting, respectively. Here we demonstrate that the C-terminus of μ1B is important for AP-1B recruitment onto recycling endosomes. We define a patch of three amino acid residues in μ1B that are necessary for recruitment of AP-1B onto recycling endosomes containing phosphatidylinositol 3,4,5-trisphosphate [PI(3,4,5)P3]. We found this lipid enriched in recycling endosomes of epithelial cells only when AP-1B is expressed. Interfering with PI(3,4,5)P3 formation leads to displacement of AP-1B from recycling endosomes and missorting of AP-1B–dependent cargo to the apical plasma membrane. In conclusion, PI(3,4,5)P3 formation in recycling endosomes is essential for AP-1B function.

scholarly journals Differential Recognition of Tyrosine-based Basolateral Signals by AP-1B Subunit μ1B in Polarized Epithelial Cells

2002 ◽  
Vol 13 (7) ◽  
pp. 2374-2382 ◽  
Author(s):  
Hisashi Sugimoto ◽  
Masayuki Sugahara ◽  
Heike Fölsch ◽  
Yasuhiro Koide ◽  
Fubito Nakatsu ◽  
...  
Keyword(s):  
Membrane Proteins ◽  
Epithelial Cells ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Mutant Form ◽  
Targeting Signals ◽  
Polarized Epithelial Cells ◽  
Clathrin Adaptor ◽  
Basolateral Targeting

To investigate the importance of tyrosine recognition by the AP-1B clathrin adaptor subunit μ1B for basolateral sorting of integral membrane proteins in polarized epithelial cells, we have produced and characterized a mutant form of μ1B. The mutant (M-μ1B) contains alanine substitutions of each of the four conserved residues, which in the AP-2 adaptor subunit μ2 are critical for interacting with tyrosine-based endocytosis signals. We show M-μ1B is defective for tyrosine binding in vitro, but is nevertheless incorporated into AP-1 complexes in transfected cells. Using LLC-PK1 cells expressing either wild type or M-μ1B, we find that there is inefficient basolateral expression of membrane proteins whose basolateral targeting signals share critical tyrosines with signals for endocytosis. In contrast, membrane proteins whose basolateral targeting signals are distinct from their endocytosis signals (transferrin and low-density lipoprotein receptors) accumulate at the basolateral domain normally, although in a manner that is strictly dependent on μ1B or M-μ1B expression. Our results suggest that μ1B interacts with different classes of basolateral targeting signals in distinct ways.

scholarly journals ARH cooperates with AP-1B in the exocytosis of LDLR in polarized epithelial cells

2011 ◽  
Vol 193 (1) ◽  
pp. 51-60 ◽  
Author(s):  
Richard S. Kang ◽  
Heike Fölsch
Keyword(s):  
Epithelial Cells ◽  
Autosomal Recessive ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipoprotein Receptors ◽  
Recycling Endosomes ◽  
Sorting Motif ◽  
Polarized Epithelial Cells ◽  
Clathrin Adaptor ◽  
Autosomal Recessive Hypercholesterolemia

The autosomal recessive hypercholesterolemia protein (ARH) is well known for its role in clathrin-mediated endocytosis of low-density lipoprotein receptors (LDLRs). During uptake, ARH directly binds to the FxNPxY signal in the cytoplasmic tail of LDLR. Interestingly, the same FxNPxY motif is used in basolateral exocytosis of LDLR from recycling endosomes (REs), which is facilitated by the epithelial-specific clathrin adaptor AP-1B. However, AP-1B directly interacts with neither the FxNPxY motif nor the second more distally located YxxØ sorting motif of LDLR. Here, we show that ARH colocalizes and cooperates with AP-1B in REs. Knockdown of ARH in polarized epithelial cells leads to specific apical missorting of truncated LDLR, which encodes only the FxNPxY motif (LDLR-CT27). Moreover, a mutation in ARH designed to disrupt the interaction of ARH with AP-1B specifically abrogates exocytosis of LDLR-CT27. We conclude that in addition to its role in endocytosis, ARH cooperates with AP-1B in basolateral exocytosis of LDLR from REs.

scholarly journals A Novel Clathrin Adaptor Complex Mediates Basolateral Targeting in Polarized Epithelial Cells

Cell ◽  
1999 ◽  
Vol 99 (2) ◽  
pp. 189-198 ◽  
Author(s):  
Heike Fölsch ◽  
Hiroshi Ohno ◽  
Juan S Bonifacino ◽  
Ira Mellman
Keyword(s):  
Epithelial Cells ◽  
Polarized Epithelial Cells ◽  
Clathrin Adaptor ◽  
Basolateral Targeting

scholarly journals The MAL Protein, an Integral Component of Specialized Membranes, in Normal Cells and Cancer

Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1065
Author(s):  
Armando Rubio-Ramos ◽  
Leticia Labat-de-Hoz ◽  
Isabel Correas ◽  
Miguel A. Alonso
Keyword(s):  
Epithelial Cells ◽  
Large Body ◽  
Original Description ◽  
Cell Types ◽  
Future Research ◽  
Transmembrane Segments ◽  
Epsilon Toxin ◽  
Proteolipid Proteins ◽  
Polarized Epithelial Cells

The MAL gene encodes a 17-kDa protein containing four putative transmembrane segments whose expression is restricted to human T cells, polarized epithelial cells and myelin-forming cells. The MAL protein has two unusual biochemical features. First, it has lipid-like properties that qualify it as a member of the group of proteolipid proteins. Second, it partitions selectively into detergent-insoluble membranes, which are known to be enriched in condensed cell membranes, consistent with MAL being distributed in highly ordered membranes in the cell. Since its original description more than thirty years ago, a large body of evidence has accumulated supporting a role of MAL in specialized membranes in all the cell types in which it is expressed. Here, we review the structure, expression and biochemical characteristics of MAL, and discuss the association of MAL with raft membranes and the function of MAL in polarized epithelial cells, T lymphocytes, and myelin-forming cells. The evidence that MAL is a putative receptor of the epsilon toxin of Clostridium perfringens, the expression of MAL in lymphomas, the hypermethylation of the MAL gene and subsequent loss of MAL expression in carcinomas are also presented. We propose a model of MAL as the organizer of specialized condensed membranes to make them functional, discuss the role of MAL as a tumor suppressor in carcinomas, consider its potential use as a cancer biomarker, and summarize the directions for future research.

scholarly journals Delivery of Na+,K(+)-ATPase in polarized epithelial cells

Science ◽  
1993 ◽  
Vol 260 (5107) ◽  
pp. 550-552 ◽  
Author(s):  
C Zurzolo ◽  
E Rodriguez-Boulan
Keyword(s):  
Epithelial Cells ◽  
Polarized Epithelial Cells
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