scholarly journals Regulation of caveolae through cholesterol-depletion-dependent tubulation mediated by PACSIN2

2020 ◽  
Vol 133 (19) ◽  
pp. jcs246785 ◽  
Author(s):  
Aini Gusmira ◽  
Kazuhiro Takemura ◽  
Shin Yong Lee ◽  
Takehiko Inaba ◽  
Kyoko Hanawa-Suetsugu ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Lipid Composition ◽  
Cholesterol Depletion ◽  
Membrane Deformation ◽  
Bar Domain ◽  
Caveolin 1 ◽  
Membrane Tubulation ◽  
Reconstituted Membranes ◽  
Shaping Ability

ABSTRACTThe membrane-shaping ability of PACSIN2 (also known as syndapin II), which is mediated by its F-BAR domain, has been shown to be essential for caveolar morphogenesis, presumably through the shaping of the caveolar neck. Caveolar membranes contain abundant cholesterol. However, the role of cholesterol in PACSIN2-mediated membrane deformation remains unclear. Here, we show that the binding of PACSIN2 to the membrane can be negatively regulated by cholesterol. We prepared reconstituted membranes based on the lipid composition of caveolae. The reconstituted membrane with cholesterol had a weaker affinity for the F-BAR domain of PACSIN2 than a membrane without cholesterol. Consistent with this, upon depletion of cholesterol from the plasma membrane, PACSIN2 localized at tubules that had caveolin-1 at their tips, suggesting that cholesterol inhibits membrane tubulation mediated by PACSIN2. The tubules induced by PACSIN2 could be representative of an intermediate of caveolae endocytosis. Consistent with this, the removal of caveolae from the plasma membrane upon cholesterol depletion was diminished in the PACSIN2-deficient cells. These data suggest that PACSIN2-mediated caveolae internalization is dependent on the amount of cholesterol, providing a mechanism for cholesterol-dependent regulation of caveolae.This article has an associated First Person interview with the first author of the paper.

scholarly journals Regulation of caveolae through cholesterol-depletion dependent tubulation by PACSIN2/Syndapin II

2020 ◽  
Author(s):  
Aini Gusmira Amir ◽  
Kazuhiro Takemura ◽  
Kyoko Hanawa-Suetsugu ◽  
Kayoko Oono-Yakura ◽  
Kazuma Yasuhara ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Lipid Composition ◽  
Electrostatic Charge ◽  
Cholesterol Depletion ◽  
Membrane Deformation ◽  
Bar Domain ◽  
Caveolin 1 ◽  
Membrane Tubulation ◽  
Shaping Ability

AbstractThe membrane shaping ability of PACSIN2 via its FCH-BAR (F-BAR) domain has been shown to be essential for caveolar morphogenesis, presumably through the shaping of the caveolar neck. Caveolar membrane contains abundant levels of cholesterol. However, the role of cholesterol in PACSIN2-mediated membrane deformation remains unclear. We show that the binding of PACSIN2 to the membrane could be negatively regulated by the amount of cholesterol in the membrane. We prepared a reconstituted membrane based on the lipid composition of caveolae. The reconstituted membrane with cholesterol had a weaker affinity to the F-BAR domain of PACSIN2 than the membrane without cholesterol, presumably due to a decrease in electrostatic charge density. Consistently, the acute depletion of cholesterol from the plasma membrane resulted in the appearance of PACSIN2-localized tubules with caveolin-1 at their tips, suggesting that the presence of cholesterol inhibited the prominent membrane tubulation by PACSIN2. The tubules induced by PACSIN2 were suggested to be an intermediate of caveolae endocytosis. Consistently, the removal of caveolae from the plasma membrane upon cholesterol depletion was diminished in the cells deficient in PACSIN2. These data suggested that PACSIN2 mediated the caveolae internalization dependently on the amount of cholesterol at the plasma membrane, providing a possible mechanism for the cholesterol-dependent regulation of caveolae.

scholarly journals Coordination between the actin cytoskeleton and membrane deformation by a novel membrane tubulation domain of PCH proteins is involved in endocytosis

2006 ◽  
Vol 172 (2) ◽  
pp. 269-279 ◽  
Author(s):  
Kazuya Tsujita ◽  
Shiro Suetsugu ◽  
Nobunari Sasaki ◽  
Masahiro Furutani ◽  
Tsukasa Oikawa ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Actin Cytoskeleton ◽  
Early Stage ◽  
Family Members ◽  
Protein Family ◽  
Membrane Deformation ◽  
Bar Domain ◽  
Cellular Processes ◽  
Cytoskeleton Reorganization ◽  
Membrane Tubulation

The conserved FER-CIP4 homology (FCH) domain is found in the pombe Cdc15 homology (PCH) protein family members, including formin-binding protein 17 (FBP17). However, the amino acid sequence homology extends beyond the FCH domain. We have termed this region the extended FC (EFC) domain. We found that FBP17 coordinated membrane deformation with actin cytoskeleton reorganization during endocytosis. The EFC domains of FBP17, CIP4, and other PCH protein family members show weak homology to the Bin-amphiphysin-Rvs (BAR) domain. The EFC domains bound strongly to phosphatidylserine and phosphatidylinositol 4,5-bisphosphate and deformed the plasma membrane and liposomes into narrow tubules. Most PCH proteins possess an SH3 domain that is known to bind to dynamin and that recruited and activated neural Wiskott-Aldrich syndrome protein (N-WASP) at the plasma membrane. FBP17 and/or CIP4 contributed to the formation of the protein complex, including N-WASP and dynamin-2, in the early stage of endocytosis. Furthermore, knockdown of endogenous FBP17 and CIP4 impaired endocytosis. Our data indicate that PCH protein family members couple membrane deformation to actin cytoskeleton reorganization in various cellular processes.

scholarly journals Caveolae/raft-dependent endocytosis

2003 ◽  
Vol 161 (4) ◽  
pp. 673-677 ◽  
Author(s):  
Ivan R. Nabi ◽  
Phuong U. Le
Keyword(s):  
Endocytic Pathway ◽  
Regulatory Role ◽  
Cholesterol Depletion ◽  
Common Pathway ◽  
Caveolin 1 ◽  
Distinctive Morphology

Although caveolae are well-characterized subdomains of glycolipid rafts, their distinctive morphology and association with caveolins has led to their internalization being considered different from that of rafts. In this review, we propose that caveolae and rafts are internalized via a common pathway, caveolae/raft-dependent endocytosis, defined by its clathrin independence, dynamin dependence, and sensitivity to cholesterol depletion. The regulatory role of caveolin-1 and ligand sorting in this complex endocytic pathway are specifically addressed.

scholarly journals Cell Surface Orifices of Caveolae and Localization of Caveolin to the Necks of Caveolae in Adipocytes

2003 ◽  
Vol 14 (10) ◽  
pp. 3967-3976 ◽  
Author(s):  
Hans Thorn ◽  
Karin G. Stenkula ◽  
Margareta Karlsson ◽  
Unn Örtegren ◽  
Fredrik H. Nystrom ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Cell Surface ◽  
Human Fibroblasts ◽  
High Resolution Electron Microscopy ◽  
Proximal Region ◽  
Cholesterol Depletion ◽  
Caveolin 1 ◽  
Resolution Electron ◽  
20 Nm ◽  
Membrane Proximal Region

Caveolae are noncoated invaginations of the plasma membrane that form in the presence of the protein caveolin. Caveolae are found in most cells, but are especially abundant in adipocytes. By high-resolution electron microscopy of plasma membrane sheets the detailed structure of individual caveolae of primary rat adipocytes was examined. Caveolin-1 and -2 binding was restricted to the membrane proximal region, such as the ducts or necks attaching the caveolar bulb to the membrane. This was confirmed by transfection with myc-tagged caveolin-1 and -2. Essentially the same results were obtained with human fibroblasts. Hence caveolin does not form the caveolar bulb in these cells, but rather the neck and may thus act to retain the caveolar constituents, indicating how caveolin participates in the formation of caveolae. Caveolae, randomly distributed over the plasma membrane, were very heterogeneous, varying in size between 25 and 150 nm. There was about one million caveolae in an adipocyte, which increased the surface area of the plasma membrane by 50%. Half of the caveolae, those larger than 50 nm, had access to the outside of the cell via ducts and 20-nm orifices at the cell surface. The rest of the caveolae, those smaller than 50 nm, were not open to the cell exterior. Cholesterol depletion destroyed both caveolae and the cell surface orifices.

scholarly journals Palmitoylation-dependent Estrogen Receptor α Membrane Localization: Regulation by 17β-Estradiol

2005 ◽  
Vol 16 (1) ◽  
pp. 231-237 ◽  
Author(s):  
Filippo Acconcia ◽  
Paolo Ascenzi ◽  
Alessio Bocedi ◽  
Enzo Spisni ◽  
Vittorio Tomasi ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Estrogen Receptor ◽  
Plasma Membrane ◽  
Estrogen Receptor Α ◽  
Membrane Localization ◽  
Target Cells ◽  
Dependent Manner ◽  
Caveolin 1 ◽  
17Β Estradiol

A fraction of the nuclear estrogen receptor α (ERα) is localized to the plasma membrane region of 17β-estradiol (E2) target cells. We previously reported that ERα is a palmitoylated protein. To gain insight into the molecular mechanism of ERα residence at the plasma membrane, we tested both the role of palmitoylation and the impact of E2 stimulation on ERα membrane localization. The cancer cell lines expressing transfected or endogenous human ERα (HeLa and HepG2, respectively) or the ERα nonpalmitoylable Cys447Ala mutant transfected in HeLa cells were used as experimental models. We found that palmitoylation of ERα enacts ERα association with the plasma membrane, interaction with the membrane protein caveolin-1, and nongenomic activities, including activation of signaling pathways and cell proliferation (i.e., ERK and AKT activation, cyclin D1 promoter activity, DNA synthesis). Moreover, E2 reduces both ERα palmitoylation and its interaction with caveolin-1, in a time- and dose-dependent manner. These data point to the physiological role of ERα palmitoylation in the receptor localization to the cell membrane and in the regulation of the E2-induced cell proliferation.

scholarly journals Effects of ATP9A on Extracellular Vesicle Release and Exosomal Lipid Composition

2020 ◽  
Vol 2020 ◽  
pp. 1-17
Author(s):  
Xiao Xu ◽  
Limei Xu ◽  
Peng Zhang ◽  
Kan Ouyang ◽  
Yin Xiao ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Extracellular Vesicles ◽  
Lipid Composition ◽  
Extracellular Vesicle ◽  
Biological Processes ◽  
Vesicle Release ◽  
Endosomal Recycling ◽  
Intracellular Compartments ◽  
Intercellular Communications

Numerous biological processes are regulated by the intercellular communications arising from extracellular vesicles (EVs) released from cells. However, the mechanisms that regulate the quantity of EV discharged have yet to be understood. While it is known that ATP9A, a P4-ATPase, is involved in endosomal recycling, it is not clear whether it also contributes to the release of EVs and the makeup of exosomal lipids. This study is aimed at exploring the role of human ATP9A in the process of EV release and, further, to analyze the profiles of EV lipids regulated by ATP9A. Our results demonstrate that ATP9A is located in both the intracellular compartments and the plasma membrane. The percentage of ceramides and sphingosine was found to be significantly greater in the control cells than in the ATP9A overexpression and ATP9A knockout groups. However, EV release was greater in ATP9A knockout cells, indicating that ATP9A inhibits the release of EVs. This study revealed the effects of ATP9A on the release of EVs and the lipid composition of exosomes.

scholarly journals Dimerization is necessary for MIM-mediated membrane deformation and endocytosis

2012 ◽  
Vol 446 (3) ◽  
pp. 469-475 ◽  
Author(s):  
Meng Cao ◽  
Tailan Zhan ◽  
Min Ji ◽  
Xi Zhan
Keyword(s):  
Metastasis Suppressor ◽  
Intracellular Protein ◽  
High Potency ◽  
Membrane Deformation ◽  
Bar Domain ◽  
Membrane Protrusions ◽  
Metastasis Suppressor 1 ◽  
Intrinsic Capacity ◽  
Transferrin Uptake

MIM [missing in metastasis; also called MTSS1 (metastasis suppressor 1)] is an intracellular protein that binds to actin and cortactin and has an intrinsic capacity to sense and facilitate the formation of protruded membranous curvatures implicated in cell-ular polarization, mobilization and endocytosis. The N-terminal 250 amino acids of MIM undergo homodimerization and form a structural module with the characteristic of an I-BAR [inverse BAR (Bin/amphiphysin/Rvs)] domain. To discern the role of the dimeric configuration in the function of MIM, we designed several peptides able to interfere with MIM dimerization in a manner dependent upon their lengths. Overexpression of one of the peptides effectively abolished MIM-mediated membrane protrusions and transferrin uptake. However, a peptide with a high potency inhibiting MIM dimerization failed to affect its binding to actin and cortactin. Thus the results of the present study indicate that the dimeric configuration is essential for MIM-mediated membrane remodelling and serves as a proper target to develop antagonists specifically against an I-BAR-domain-containing protein.

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