共查询到20条相似文献,搜索用时 734 毫秒
1.
Seaman MN 《Cellular and molecular life sciences : CMLS》2008,65(18):2842-2858
The steady-state localisation of membrane proteins in the endocytic system is the result of many sorting events that occur
at various points throughout the endosomal pathway. A protein that has been endocytosed from the plasma membrane or sorted
at the trans-Golgi network (TGN) and transported to an endosome will ultimately be delivered to one of three destinations:
the plasma membrane, the TGN or the lysosome. Where a membrane protein is trafficked to depends on the interactions between
sorting motifs present in the membrane protein and the machinery that can decode these motifs. Much of the protein machinery
that recognises sorting motifs is conserved from yeast toman, and in this review I will discuss this machinery and the motifs
that govern endosomal protein sorting. (Part of a Multi-author Review) 相似文献
2.
Chiow KH Tan Y Chua RY Huang D Ng ML Torta F Wenk MR Wong SH 《Cellular and molecular life sciences : CMLS》2012,69(9):1505-1521
Since being introduced globally as aspirin in 1899, acetylsalicylic acid has been widely used as an analgesic, anti-inflammation,
anti-pyretic, and anti-thrombotic drug for years. Aspirin had been reported to down-regulate surface expression of CD40, CD80,
CD86, and MHCII in myeloid dendritic cells (DC), which played essential roles in regulating the immune system. We hypothesized
that the down-regulation of these surface membrane proteins is partly due to the ability of aspirin in regulating trafficking/sorting
of endocytosed surface membrane proteins. By using an established epidermoid carcinoma cell line (A-431), which overexpresses
the epidermal growth factor receptor (EGFR) and transferrin receptor (TfnR), we show that aspirin (1) reduces cell surface
expression of EGFR and (2) accumulates endocytosed-EGFR and -TfnR in the early/sorting endosome (ESE). Further elucidation
of the mechanism suggests that aspirin enhances recruitment of SNX3 and SNX5 to membranes and consistently, both SNX3 and
SNX5 play essential roles in the aspirin-mediated accumulation of endocytosed-TfnR at the ESE. This study sheds light on how
aspirin may down-regulate surface expression of EGFR by inhibiting/delaying the exit of endocytosed-EGFR from the ESE and
recycling of endocytosed-EGFR back to the cell surface. 相似文献
3.
Corda D Hidalgo Carcedo C Bonazzi M Luini A Spanò S 《Cellular and molecular life sciences : CMLS》2002,59(11):1819-1832
Membrane fission is essential in various intracellular dissociative transport steps. The molecular mechanisms by which endocytic
vesicles detach from the plasma membrane are being rapidly elucidated. Much less is known about the fission mechanisms operating
at Golgi tubular networks; these include the Golgi transport and sorting stations, the trans-Golgi and cis-Golgi networks,
where the geometry and physical properties of the membranes differ from those at the cell surface. Here we discuss the lipid
and protein machineries that have so far been related to the fission process, with emphasis on those acting in the Golgi complex.
Received 10 May 2002; received after revision 20 June 2002; accepted 26 June 2002
RID="*"
ID="*"Corresponding author. 相似文献
4.
Terhi Vihervaara Riikka-Liisa Uronen Gerd Wohlfahrt Ingemar Björkhem Elina Ikonen Vesa M. Olkkonen 《Cellular and molecular life sciences : CMLS》2011,68(3):537-551
ORP1L is an oxysterol binding homologue that regulates late endosome (LE) positioning. We show that ORP1L binds several oxysterols
and cholesterol, and characterize a mutant, ORP1L Δ560–563, defective in oxysterol binding. While wild-type ORP1L clusters
LE, ORP1L Δ560–563 induces LE scattering, which is reversed by disruption of the endoplasmic reticulum (ER) targeting FFAT
motif, suggesting that it is due to enhanced LE–ER interactions. Endosome motility is reduced upon overexpression of ORP1L.
Both wild-type ORP1L and the Δ560–563 mutant induce the recruitment of both dynactin and kinesin-2 on LE. Most of the LE decorated
by overexpressed ORP1L fail to accept endocytosed dextran or EGF, and the transfected cells display defective degradation
of internalized EGF. ORP1L silencing in macrophage foam cells enhances endosome motility and results in inhibition of [3H]cholesterol efflux to apolipoprotein A-I. These data demonstrate that LE motility and functions in both protein and lipid
transport are regulated by ORP1L. 相似文献
5.
Ernst S Zobiack N Boecker K Gerke V Rescher U 《Cellular and molecular life sciences : CMLS》2004,61(13):1684-1692
The formyl peptide-like receptor FPRL1 is a member of the chemoattractant subfamily of G protein- coupled receptors involved in regulating leukocyte migration in inflammation. To elucidate mechanisms underlying the internalization of ligand-bound FPRL1 and possible receptor recycling, we characterized the endocytic itinerary of FPRL1. We show that agonist-triggered internalization from the plasma membrane into intracellular compartments is prevented by perturbation of clathrin-mediated endocytosis, such as expression of the dominant-negative clathrin Hub mutant, siRNA-mediated depletion of cellular clathrin and expression of a dominant-negative mutant of the large GTPase dynamin. Internalized FPRL1 co-localized with endocytosed transferrin and the small GTPases Rab4 and Rab11 in vesicular structures most resembling recycling endosomes. Recycling of FPRL1 was significantly reduced by pretreatment with PI3-kinase inhibitors. Thus, ligand-bound FPRL1 undergoes primarily clathrin-mediated and dynamin-dependent endocytosis and the receptor recycles via a rapid PI3-kinase-sensitive route as well as pathways involving perinuclear recycling endosomes.Received 19 March 2004; received after revision 26 April 2004; accepted 12 May 2004 相似文献
6.
The plasma membrane of epithelial cells and hepatocytes is divided into two separate membrane compartments, the apical and
the basolateral domain. This polarity is maintained by intracellular machinery that directs newly synthesized material into
the correct target membrane. Apical protein sorting and trafficking require specific signals and different intracellular routes
to the cell surface. Some of them depend on the integrity of sphingolipid/cholesterol-enriched membrane microdomains named
‘lipid rafts’, others use separate transport platforms. Certain characteristics of the heterogeneous population of apical
sorting signals are described in this review and cellular factors associated with sorting and transport mechanisms are discussed.
Received 5 May 2006; received after revision 12 June 2006; accepted 11 July 2006 相似文献
7.
Dong Wang Chih-Chiang Chan Smita Cherry P. Robin Hiesinger 《Cellular and molecular life sciences : CMLS》2013,70(16):2919-2934
Defects in membrane trafficking and degradation are hallmarks of most, and maybe all, neurodegenerative disorders. Such defects typically result in the accumulation of undegraded proteins due to aberrant endosomal sorting, lysosomal degradation, or autophagy. The genetic or environmental cause of a specific disease may directly affect these membrane trafficking processes. Alternatively, changes in intracellular sorting and degradation can occur as cellular responses of degenerating neurons to unrelated primary defects such as insoluble protein aggregates or other neurotoxic insults. Importantly, altered membrane trafficking may contribute to the pathogenesis or indeed protect the neuron. The observation of dramatic changes to membrane trafficking thus comes with the challenging need to distinguish pathological from protective alterations. Here, we will review our current knowledge about the protective and destructive roles of membrane trafficking in neuronal maintenance and degeneration. In particular, we will first focus on the question of what type of membrane trafficking keeps healthy neurons alive in the first place. Next, we will discuss what alterations of membrane trafficking are known to occur in Alzheimer’s disease and other tauopathies, Parkinson’s disease, polyQ diseases, peripheral neuropathies, and lysosomal storage disorders. Combining the maintenance and degeneration viewpoints may yield insight into how to distinguish when membrane trafficking functions protectively or contributes to degeneration. 相似文献
8.
BCL2-associated athanogene 6 (BAG-6) (also Bat-3/Scythe) was discovered as a gene product of the major histocompatibility complex class III locus. The Xenopus ortholog Scythe was first identified to act as an anti-apoptotic protein. Subsequent studies unraveled that the large BAG-6 protein contributes to a number of cellular processes, including apoptosis, gene regulation, protein synthesis, protein quality control, and protein degradation. In this context, BAG-6 acts as a multifunctional chaperone, which interacts with its target proteins for shuttling to distinct destinations. Nonetheless, as anticipated from its genomic localization, BAG-6 is involved in a variety of immunological pathways such as macrophage function and TH1 response. Most recently, BAG-6 was identified on the plasma membrane of dendritic cells and malignantly transformed cells where it serves as cellular ligand for the activating natural killer (NK) cell receptor NKp30 triggering NK cell cytotoxicity. Moreover, target cells were found to secrete soluble variants of BAG-6 and release BAG-6 on the surface of exosomes, which inhibit or activate NK cell cytotoxicity, respectively. These data suggest that the BAG-6 antigen is an important target to shape a directed immune response or to overcome tumor-immune escape strategies established by soluble BAG-6. This review summarizes the currently known functions of BAG-6, a fascinating multicompetent protein, in health and disease. 相似文献
9.
This review presents plant-specific characteristics of the Golgi apparatus and discusses their impact on retention of membrane proteins in the Golgi or the trans-Golgi network (TGN). The plant Golgi consists of distinct stacks of cisternae that actively move throughout the cytoplasm. The Golgi apparatus is a very dynamic compartment and the site for maturation of N-linked glycans. It is also a factory for complex carbohydrates that are part of the cell wall. The TGN is believed to be the site from where vacuolar proteins are sorted by receptors towards each type of vacuole. To maintain the structure and specific features of the Golgi, resident proteins ought to be maintained in the proper Golgi cisternae or in the TGN. Two families of membrane proteins will be taken as examples for Golgi/TGN retention: (i) the enzymes involved in N-glycosylation processes and (ii) a vacuolar sorting receptor. Although the number of available plant proteins localized in Golgi/TGN is low, the basis of retention appears to be shared over all kingdoms and may result from pure retention and recycling mechanisms. In this review, we will summarize the characteristics of a plant Golgi and will discuss especially their consequences on on the study of this highly dynamic structure. We then choose membrane proteins with a single transmembrane domain to illustrate the signals and mechanisms involved in plants to localize and maintain proteins in the Golgi and the TGN. 相似文献
10.
Nolwenn Jouvenet 《Cellular and molecular life sciences : CMLS》2012,69(24):4121-4133
Proteins of the ESCRT (endosomal sorting complex required for transport) complex function in membrane fission processes, such as multivesicular body (MVBs) formation, the terminal stages of cytokinesis, and separation of enveloped viruses from the plasma membrane. In mammalian cells, the machinery consists of a network of more than 20?proteins, organized into three complexes (ESCRT-I, -II, and -III), and other associated proteins such as the ATPase vacuolar protein sorting 4 (Vps4). Early biochemical studies of MVBs biogenesis in yeast support a model of sequential recruitment of ESCRT complexes on membranes. Live-cell imaging of ESCRT protein dynamics during viral budding and cytokinesis now reveal that this long-standing model of sequential assembly and disassembly holds true in mammalian cells. 相似文献
11.
Aamir S. Mukadam Sophia Y. Breusegem Matthew N. J. Seaman 《Cellular and molecular life sciences : CMLS》2018,75(14):2613-2625
The processing of amyloid precursor protein (APP) to the neurotoxic pro-aggregatory Aβ peptide is controlled by the mechanisms that govern the trafficking and localisation of APP. We hypothesised that genes involved in endosomal protein sorting could play an important role in regulating APP processing and, therefore, analysed ~ 40 novel endosome-to-Golgi retrieval genes previously identified in a genome-wide siRNA screen. We report that phospholipase D3 (PLD3), a type II membrane protein, functions in endosomal protein sorting and plays an important role in regulating APP processing. PLD3 co-localises with APP in endosomes and loss of PLD3 function results in reduced endosomal tubules, impaired trafficking of several membrane proteins and reduced association of sortilin-like 1 with APP. 相似文献
12.
Goh YC Yap CT Huang BH Cronshaw AD Leung BP Lai PB Hart SP Dransfield I Ross JA 《Cellular and molecular life sciences : CMLS》2011,68(9):1581-1592
Heat-shock protein 60 (Hsp60) is a highly conserved stress protein which has chaperone functions in prokaryotes and mammalian
cells. Hsp60 is associated with the mitochondria and the plasma membrane through phosphorylation by protein kinase A, and
is incorporated into lipid membranes as a protein-folding chaperone. Its diverse intracellular chaperone functions include
the secretion of proteins where it maintains the conformation of precursors and facilitates their translocation through the
plasma membrane. We report here that Hsp60 is concentrated in apoptotic membrane blebs and translocates to the surface of
cells undergoing apoptosis. Hsp60 is also enriched in platelets derived from terminally differentiated megakaryocytes and
expressed at the surface of senescent platelets. Furthermore, the exposure of monocytic U937 cells to Hsp60 enhanced their
phagocytic activity. Our results suggests that externalized Hsp60 in apoptotic cells and senescent platelets influences events
subsequent to apoptosis, such as the clearance of apoptotic cells by phagocytes. 相似文献
13.
Glucagon is a pancreatic peptide hormone that, as a counterregulatory hormone for insulin, stimulates glucose release by the liver and maintains glucose homeostasis. First described as a glucagon binding entity functionally linked to adenylyl cyclase, the glucagon receptor is a member of the family B receptors within the G protein coupled superfamily of seven transmembrane-spanning receptors. During the past decade, considerable progress has been made in the identification of the molecular determinants of the glucagon receptor that are important for ligand binding and signal transduction, in the development of glucagon analogs and of nonpeptide small molecules acting as receptor antagonists, and in the characterization of the mechanisms involved in the regulation of expression of the glucagon receptor gene. In the present review, the current knowledge of glucagon receptor structure, function and expression is described, with emphasis on the metabolic fate of glucagon and on the endocytosis and cell itinerary of both ligand and receptor. 相似文献
14.
Iber D 《Cellular and molecular life sciences : CMLS》2005,62(2):206-213
Interaction of B cells with membrane antigen results in the formation of the B cell synapse: the B cell receptor (BCR) and antigen concentrate in the contact zone while CD45/B220 and the phosphatase SHP-1 are excluded. This study shows that, unlike in T cells, synapse formation does not require active transport processes (while subsequent antigen extraction and IgM downregulation do). The synapse architecture depends on the available protein ligands in the contact zone. Thus Syk, IgM and Fc receptor accumulation require the presence of ITAM-bearing BCRs, membrane antigen and membrane (IgG-containing) immune complexes, respectively. Remarkably, non-bound proteins are frequently not only homogeneously distributed but excluded from the contact zone. These results suggest that proteins mainly reach the contact zone by undirected diffusion, and in order not to be expelled by molecular crowding they require capture by and fixation to a binding protein.Received 25 August 2004; received after revision 2 November 2004; accepted 17 November 2004 相似文献
15.
Llorca O 《Cellular and molecular life sciences : CMLS》2008,65(9):1302-1310
In mammals, the mannose receptor family consists of four members, Endo180, DEC-205, phospholipase A2 receptor and the mannose receptor. The extracellular domains of all these receptors contain a similar arrangement of domains
in which an Nterminal cysteine-rich domain is followed by a single fibronectin type II domain and eight or ten C-type lectin-like
domains. This review focuses on the threedimensional structure of the receptors in the mannose receptor family and its functional
implication. Recent research has revealed that several members of this family can exist in at least two configurations: an
extended conformation with the N-terminal cysteinerich domain pointing outwards from the cell membrane and a bent conformation
where the N-terminal domains fold back to interact with C-type lectin-like domains at the middle of the structure. Conformational
transitions between these two states seem to regulate the interaction of these receptors with ligands and their oligomerization.
Received 25 October 2007; received after revision 23 November 2007; accepted 7 December 2007 相似文献
16.
Endogenous opioids have been studied extensively since their discovery, in the hope of finding a perfect analgesic, devoid
of the secondary effects of alkaloid opioids. However, the design of selective opioid agonists has proved very difficult.
First, structural studies of peptides in general are hampered by their intrinsic flexibility. Second, the relationship between
constitution and the so-called 'bioactive conformation' is far from obvious. Ideally, a direct structural study of the complex
between a peptide and its receptor should answer both questions, but such a study is not possible, because opioid receptors
are large membrane proteins, difficult to study by standard structural techniques. Thus, conformational studies of opioid
peptides are still important for drug design and also for indirect receptor mapping. This review deals with conformational
studies of natural opioid peptides in several solvents that mimic in part the different environments in which the peptides
exert their action. None of the structural investigations yields a convincing bioactive conformation, but the global conformation
of longer peptides in biomimetic environments can shed light on the interaction with receptors.
Received 15 April 2001; received after revision 10 May 2001; accepted 11 May 2001 相似文献
17.
Functions of the MDM2 oncoprotein 总被引:34,自引:1,他引:33
18.
Harald W. Platta Stefanie Hagen Ralf Erdmann 《Cellular and molecular life sciences : CMLS》2013,70(8):1393-1411
Peroxisomes constitute a dynamic compartment of almost all eukaryotic cells. Depending on environmental changes and cellular demands peroxisomes can acquire diverse metabolic roles. The compartmentalization of peroxisomal matrix enzymes is a prerequisite to carry out their physiologic function. The matrix proteins are synthesized on free ribosomes in the cytosol and are ferried to the peroxisomal membrane by specific soluble receptors. Subsequent to cargo release into the peroxisomal matrix, the receptors are exported back to the cytosol to facilitate further rounds of matrix protein import. This dislocation step is accomplished by a remarkable machinery, which comprises enzymes required for the ubiquitination as well as the ATP-dependent extraction of the receptor from the membrane. Interestingly, receptor ubiquitination and dislocation are the only known energy-dependent steps in the peroxisomal matrix protein import process. The current view is that the export machinery of the receptors might function as molecular motor not only in the dislocation of the receptors but also in the import step of peroxisomal matrix protein by coupling ATP-dependent removal of the peroxisomal import receptor with cargo translocation into the organelle. In this review we will focus on the architecture and function of the peroxisomal receptor export machinery, the peroxisomal exportomer. 相似文献
19.
A. Venerando L. Cesaro O. Marin A. Donella-Deana L. A. Pinna 《Cellular and molecular life sciences : CMLS》2014,71(12):2193-2196
The motif “SYDE”, incorporating the protein kinase CK2 consensus sequence (S-x-x-E) has been found to be phosphorylated at both its serine and tyrosine residues in several proteins. Of special interest is the case of cystic fibrosis Transmembrane-conductance Regulator (CFTR), where this motif is close to the residue (F508), whose deletion is the by far commonest cause of cystic fibrosis. Intriguingly, however, CFTR S511 cannot be phosphorylated by CK2 to any appreciable extent. Using a number of peptide substrates encompassing the CFTR “SYDE” site we have recently shown that: (1) failure of CK2 to phosphorylate the S511YDE motif is due to the presence of Y512; (2) CK2 readily phosphorylates S511 if Y512 is replaced by a phospho-tyrosine; (3) the Src family protein tyrosine kinase Lyn phosphorylates Y512 in a manner that is enhanced by the deletion of F508. These data, in conjunction with the recent observation that by inhibiting CK2 the degradation of F508delCFTR is reduced, lead us to hypothesize that the hierarchical phosphorylation of the motif SYDE by the concerted action of protein tyrosine kinases and CK2 is one of the mechanisms that cooperate to the premature degradation of F508delCFTR. 相似文献
20.
The trans-Golgi network (TGN) is a major secretory pathway sorting station that directs newly synthesized proteins to different
subcellular destinations. The TGN also receives extracellular materials and recycled molecules from endocytic compartments.
In this review, we summarize recent progress on understanding TGN structure and the dynamics of trafficking to and from this
compartment. Protein sorting into different transport vesicles requires specific interactions between sorting motifs on the
cargo molecules and vesicle coat components that recognize these motifs. Current understanding of the various targeting signals
and vesicle coat components that are involved in TGN sorting are discussed, as well as the molecules that participate in retrieval
to this compartment in both yeast and mammalian cells. Besides proteins, lipids and lipid-modifying enzymes also participate
actively in the formation of secretory vesicles. The possible mechanisms of action of these lipid hydrolases and lipid kinases
are discussed. Finally, we summarize the fundamentally different apical and basolateral cell surface delivery mechanisms and
the current facts and hypotheses on protein sorting from the TGN into the regulated secretory pathway in neuroendocrine cells.
Received 2 November 2000; received after revision 19 February 2001; accepted 19 February 2001 相似文献