scholarly journals Lipid raft abnormalities and subsequent protein trafficking effects in Niemann‐Pick type C1 (LB158)

2014 ◽  
Vol 28 (S1) ◽  
Author(s):  
Eva‐Maria Kuech ◽  
Hadeel Shammas ◽  
Katia E. Maalouf ◽  
Maren Koeckritz‐Blickwede ◽  
Anibh M. Das ◽  
...  
Keyword(s):  
Lipid Raft ◽  
Protein Trafficking ◽  
Niemann Pick

scholarly journals Glucosylhydroxyceramides Modulate Secretion Machinery of a Subset of Plasmodesmata Proteins and a Change in the Callose Accumulation

2020 ◽  
Author(s):  
Arya Bagus Boedi Iswanto ◽  
Jong Cheol Shon ◽  
Minh Huy Vu ◽  
Ritesh Kumar ◽  
Kwang Hyeon Liu ◽  
...  
Keyword(s):  
Membrane Protein ◽  
Lipid Rafts ◽  
Lipid Raft ◽  
Protein Trafficking ◽  
Intracellular Trafficking ◽  
Plasma Membranes ◽  
Sphingolipid Metabolism ◽  
Callose Deposition ◽  
Membrane Protein Trafficking ◽  
Underlying Processes

AbstractThe plasma membranes encapsulated in the plasmodesmata (PDs) with symplasmic nano-channels contain abundant lipid rafts, which are enriched by sphingolipids and sterols. The attenuation of sterol compositions has demonstrated the role played by lipid raft integrity in the intercellular trafficking of glycosylphosphatidylinositol (GPI)-anchored PD proteins, particularly affecting in the callose enhancement. The presence of callose at PD is tightly attributed to the callose metabolic enzymes, callose synthases (CalSs) and β-1,3-glucanases (BGs) in regulating callose accumulation and callose degradation, respectively. Sphingolipids have been implicated in signaling and membrane protein trafficking, however the underlying processes linking sphingolipid compositions to the control of symplasmic apertures remain unknown. A wide variety of sphingolipids in plants prompts us to investigate which sphingolipid molecules are important in regulating symplasmic apertures. Here, we demonstrate that perturbations of sphingolipid metabolism by introducing several potential sphingolipid (SL) pathway inhibitors and genetically modifying SL contents from two independent SL pathway mutants are able to modulate callose deposition to control symplasmic connectivity. Our data from pharmacological and genetic approaches show that the alteration in glucosylhydroxyceramides (GlcHCers) particularly disturb the secretory machinery for GPI-anchored PdBG2 protein, resulting in an over accumulated callose. Moreover, our results reveal that SL-enriched lipid rafts link symplasmic channeling to PD callose homeostasis by controlling the targeting of GPI-anchored PdBG2. This study elevates our understanding of the molecular linkage underlying intracellular trafficking and precise targeting to specific destination of GPI-anchored PD proteins incorporated with GlcHCers contents.

scholarly journals Bioactive dietary long-chain fatty acids: emerging mechanisms of action

2008 ◽  
Vol 100 (6) ◽  
pp. 1152-1157 ◽  
Author(s):  
Robert S. Chapkin ◽  
David N. McMurray ◽  
Laurie A. Davidson ◽  
Bhimanagouda S. Patil ◽  
Yang-Yi Fan ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Lipid Rafts ◽  
Lipid Raft ◽  
Protein Trafficking ◽  
Protein Function ◽  
Plasma Membranes ◽  
Biological Effects ◽  
Cell Signalling ◽  
Chain Pufa ◽  
Long Chain

The plasma membranes of all eukaryotic cells contain heterogeneous self-organising intrinsically unstable liquid ordered domains or lipid assemblies in which key signal transduction proteins are localised. These assemblies are classified as ‘lipid rafts’ (10–200 nm), which are composed mostly of cholesterol and sphingolipid microdomains and therefore do not integrate well into the fluid phospholipid bilayers. In addition, caveolae represent a subtype of lipid raft macrodomain that form flask-shaped membrane invaginations containing structural proteins, i.e. caveolins. With respect to the diverse biological effects of long-chain PUFA, increasing evidence suggests that n-3 PUFA and perhaps conjugated fatty acids uniquely alter the basic properties of cell membranes. Because of its polyunsaturation, DHA and possibly conjugated linoleic acid are sterically incompatible with sphingolipid and cholesterol and, therefore, appear to alter lipid raft behaviour and protein function. The present review examines the evidence indicating that dietary sources of n-3 PUFA can profoundly alter the biochemical make up of lipid rafts/caveolae microdomains, thereby influencing cell signalling, protein trafficking and cell cytokinetics.

scholarly journals Improvement in Lipid and Protein Trafficking in Niemann-Pick C1 Cells by Correction of a Secondary Enzyme Defect

Traffic ◽  
2010 ◽  
Vol 11 (5) ◽  
pp. 601-615 ◽  
Author(s):  
Cecilia Devlin ◽  
Nina H. Pipalia ◽  
Xianghai Liao ◽  
Edward H. Schuchman ◽  
Frederick R. Maxfield ◽  
...  
Keyword(s):  
Protein Trafficking ◽  
Enzyme Defect ◽  
Niemann Pick

scholarly journals Resistance to alkyl-lysophospholipid-induced apoptosis due to downregulated sphingomyelin synthase 1 expression with consequent sphingomyelin- and cholesterol-deficiency in lipid rafts

2006 ◽  
Vol 401 (2) ◽  
pp. 541-549 ◽  
Author(s):  
Arnold H. Van der Luit ◽  
Marianne Budde ◽  
Shuraila Zerp ◽  
Wendy Caan ◽  
Jeffrey B. Klarenbeek ◽  
...  
Keyword(s):  
Lipid Rafts ◽  
Lipid Raft ◽  
Physical Interaction ◽  
Sphingomyelin Synthase ◽  
Variant Cell ◽  
Niemann Pick ◽  
Induced Apoptosis ◽  
Golgi Network ◽  
Interfering Rna ◽  
Mouse Lymphoma

The ALP (alkyl-lysophospholipid) edelfosine (1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine; Et-18-OCH3) induces apoptosis in S49 mouse lymphoma cells. To this end, ALP is internalized by lipid raft-dependent endocytosis and inhibits phosphatidylcholine synthesis. A variant cell-line, S49AR, which is resistant to ALP, was shown previously to be unable to internalize ALP via this lipid raft pathway. The reason for this uptake failure is not understood. In the present study, we show that S49AR cells are unable to synthesize SM (sphingomyelin) due to down-regulated SMS1 (SM synthase 1) expression. In parental S49 cells, resistance to ALP could be mimicked by small interfering RNA-induced SMS1 suppression, resulting in SM deficiency and blockage of raft-dependent internalization of ALP and induction of apoptosis. Similar results were obtained by treatment of the cells with myriocin/ISP-1, an inhibitor of general sphingolipid synthesis, or with U18666A, a cholesterol homoeostasis perturbing agent. U18666A is known to inhibit Niemann–Pick C1 protein-dependent vesicular transport of cholesterol from endosomal compartments to the trans-Golgi network and the plasma membrane. U18666A reduced cholesterol partitioning in detergent-resistant lipid rafts and inhibited SM synthesis in S49 cells, causing ALP resistance similar to that observed in S49AR cells. The results are explained by the strong physical interaction between (newly synthesized) SM and available cholesterol at the Golgi, where they facilitate lipid raft formation. We propose that ALP internalization by lipid-raft-dependent endocytosis represents the retrograde route of a constitutive SMS1- and lipid-raft-dependent membrane vesicular recycling process.

Role of molecular chaperones in steroid receptor action

2004 ◽  
Vol 40 ◽  
pp. 41-58 ◽  
Author(s):  
William B Pratt ◽  
Mario D Galigniana ◽  
Yoshihiro Morishima ◽  
Patrick J M Murphy
Keyword(s):  
Transcriptional Activation ◽  
Protein Trafficking ◽  
Steroid Receptors ◽  
Transcriptional Regulatory ◽  
Ubiquitin Proteasome ◽  
Proteasome Pathway ◽  
Receptor Action ◽  
Binding Cleft ◽  
Hsp 90

Unliganded steroid receptors are assembled into heterocomplexes with heat-shock protein (hsp) 90 by a multiprotein chaperone machinery. In addition to binding the receptors at the chaperone site, hsp90 binds cofactors at other sites that are part of the assembly machinery, as well as immunophilins that connect the assembled receptor-hsp90 heterocomplexes to a protein trafficking pathway. The hsp90-/hsp70-based chaperone machinery interacts with the unliganded glucocorticoid receptor to open the steroid-binding cleft to access by a steroid, and the machinery interacts in very dynamic fashion with the liganded, transformed receptor to facilitate its translocation along microtubular highways to the nucleus. In the nucleus, the chaperone machinery interacts with the receptor in transcriptional regulatory complexes after hormone dissociation to release the receptor and terminate transcriptional activation. By forming heterocomplexes with hsp90, the chaperone machinery stabilizes the receptor to degradation by the ubiquitin-proteasome pathway of proteolysis.

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