scholarly journals TMEM110 regulates the maintenance and remodeling of mammalian ER–plasma membrane junctions competent for STIM–ORAI signaling

2015 ◽  
Vol 112 (51) ◽  
pp. E7083-E7092 ◽  
Author(s):  
Ariel Quintana ◽  
Vangipurapu Rajanikanth ◽  
Suzette Farber-Katz ◽  
Aparna Gudlur ◽  
Chen Zhang ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Calcium Signaling ◽  
Mammalian Cells ◽  
Calcium Release ◽  
Close Contact ◽  
Transmembrane Protein ◽  
Regulatory Protein ◽  
Major Mechanism ◽  
Genome Wide ◽  
Core Elements

The stromal interaction molecule (STIM)–ORAI calcium release-activated calcium modulator (ORAI) pathway controls store-dependent calcium entry, a major mechanism of physiological calcium signaling in mammalian cells. The core elements of the pathway are the regulatory protein STIM1, located in the endoplasmic reticulum (ER) membrane, the calcium channel ORAI1 in the plasma membrane, and sites of close contact between the ER and the plasma membrane that permit the two proteins to interact. Research on calcium signaling has centered on STIM1, ORAI1, and a few proteins that directly modulate STIM–ORAI function. However, little is known about proteins that organize ER–plasma membrane junctions for STIM–ORAI-dependent calcium signaling. Here, we report that an ER-resident membrane protein identified in a previous genome-wide RNAi screen, transmembrane protein 110 (TMEM110), regulates the long-term maintenance of ER–plasma membrane junctions and the short-term physiological remodeling of the junctions during store-dependent calcium signaling.

scholarly journals Calcium Influx and Signaling in Yeast Stimulated by Intracellular Sphingosine 1-Phosphate Accumulation

2001 ◽  
Vol 276 (15) ◽  
pp. 11712-11718 ◽  
Author(s):  
Christine J. Birchwood ◽  
Julie D. Saba ◽  
Robert C. Dickson ◽  
Kyle W. Cunningham
Keyword(s):  
Calcium Signaling ◽  
Mammalian Cells ◽  
Cellular Response ◽  
Calcium Release ◽  
Calcium Influx ◽  
Yeast Cells ◽  
Signaling Mechanism ◽  
Sphingosine 1 Phosphate ◽  
Sphingosine Kinases ◽  
S1p Lyase

In mammalian cells, intracellular sphingosine 1-phosphate (S1P) can stimulate calcium release from intracellular organelles, resulting in the activation of downstream signaling pathways. The budding yeastSaccharomyces cerevisiaeexpresses enzymes that can synthesize and degrade S1P and related molecules, but their possible role in calcium signaling has not yet been tested. Here we examine the effects of S1P accumulation on calcium signaling using a variety of yeast mutants. Treatment of yeast cells with exogenous sphingosine stimulated Ca2+accumulation through two distinct pathways. The first pathway required the Cch1p and Mid1p subunits of a Ca2+influx channel, depended upon the function of sphingosine kinases (Lcb4p and Lcb5p), and was inhibited by the functions of S1P lyase (Dpl1p) and the S1P phosphatase (Lcb3p). The biologically inactive stereoisomer of sphingosine did not activate this Ca2+influx pathway, suggesting that the active S1P isomer specifically stimulates a calcium-signaling mechanism in yeast. The second Ca2+influx pathway stimulated by the addition of sphingosine was not stereospecific, was not dependent on the sphingosine kinases, occurred only at higher doses of added sphingosine, and therefore was likely to be nonspecific. Mutants lacking both S1P lyase and phosphatase (dpl1 lcb3double mutants) exhibited constitutively high Ca2+accumulation and signaling in the absence of added sphingosine, and these effects were dependent on the sphingosine kinases. These results show that endogenous S1P-related molecules can also trigger Ca2+accumulation and signaling. Several stimuli previously shown to evoke calcium signaling in wild-type cells were examined inlcb4 lcb5double mutants. All of the stimuli produced calcium signals independent of sphingosine kinase activity, suggesting that phosphorylated sphingoid bases might serve as messengers of calcium signaling in yeast during an unknown cellular response.

scholarly journals Plasma membrane domains enriched in cortical endoplasmic reticulum function as membrane protein trafficking hubs

2013 ◽  
Vol 24 (17) ◽  
pp. 2703-2713 ◽  
Author(s):  
Philip D. Fox ◽  
Christopher J. Haberkorn ◽  
Aubrey V. Weigel ◽  
Jenny L. Higgins ◽  
Elizabeth J. Akin ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Plasma Membrane ◽  
Membrane Protein ◽  
Membrane Trafficking ◽  
Protein Trafficking ◽  
Mammalian Cells ◽  
Transmembrane Protein ◽  
Surface Proteins ◽  
Hek 293 ◽  
Cortical Endoplasmic Reticulum

In mammalian cells, the cortical endoplasmic reticulum (cER) is a network of tubules and cisterns that lie in close apposition to the plasma membrane (PM). We provide evidence that PM domains enriched in underlying cER function as trafficking hubs for insertion and removal of PM proteins in HEK 293 cells. By simultaneously visualizing cER and various transmembrane protein cargoes with total internal reflectance fluorescence microscopy, we demonstrate that the majority of exocytotic delivery events for a recycled membrane protein or for a membrane protein being delivered to the PM for the first time occur at regions enriched in cER. Likewise, we observed recurring clathrin clusters and functional endocytosis of PM proteins preferentially at the cER-enriched regions. Thus the cER network serves to organize the molecular machinery for both insertion and removal of cell surface proteins, highlighting a novel role for these unique cellular microdomains in membrane trafficking.

scholarly journals Focused ultrasound stimulates ER localized mechanosensitive PANNEXIN-1 to mediate intracellular calcium release in invasive cancer cells

2020 ◽  
Author(s):  
Nan Sook Lee ◽  
Chi Woo Yoon ◽  
Qing Wang ◽  
Sunho Moon ◽  
Kweon Mo Koo ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Calcium Signaling ◽  
Cancer Cells ◽  
Focused Ultrasound ◽  
Calcium Release ◽  
Atp Release ◽  
Invasive Cancer ◽  
Great Promise ◽  
Pannexin 1 ◽  
Cellular Processes

ABSTRACTFocused ultrasound (FUS) is a rapidly developing stimulus technology with the potential to uncover novel mechanosensory dependent cellular processes. Since it is noninvasive, it holds great promise for future therapeutic applications in patients used either alone or as a complement to boost existing treatments. For example, FUS stimulation causes invasive but not noninvasive cancer cell lines to exhibit marked activation of calcium signaling pathways. Here, we identify the membrane channel PANNEXIN1 (PANX1) as a mediator for activation of calcium signaling in invasive cancer cells. Knockdown of PANX1 decreases calcium signaling in invasive cells, while PANX1 overexpression enhances calcium elevations in non-invasive cancer cells. We demonstrate that FUS may directly stimulate mechanosensory PANX1 localized in endoplasmic reticulum to evoke calcium release from internal stores. This process does not depend on mechanosensory stimulus transduction through an intact cytoskeleton and does not depend on plasma membrane localized PANX1. Plasma membrane localized PANX1 however plays a different role in mediating the spread of intercellular calcium waves via ATP release. Additionally, we show that FUS stimulation evokes cytokine/chemokine release from invasive cancer cells, suggesting that FUS could be an important new adjuvant treatment to improve cancer immunotherapy.

Mechanism of Selectivity of Arsenic Trioxide for Acute Promyelocytic Leukemia Cells from Screening a Genome Wide Set of Saccharomyces cerevisiae Deletion Strains.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2470-2470
Author(s):  
Pierre J. Dilda ◽  
Gabriel G. Perrone ◽  
Ian W. Dawes ◽  
Philip J. Hogg
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Plasma Membrane ◽  
Retinoic Acid ◽  
Fusion Protein ◽  
Arsenic Trioxide ◽  
Mammalian Cells ◽  
Hog Pathway ◽  
Genome Wide ◽  
A Genome ◽  
Mapk Signalling

Abstract All-trans retinoic acid (ATRA) targets the underlying molecular lesion in acute promyelocytic leukaemia (APL) and leads to differentiation of leukemic blasts into mature granulocytes. Treatment with ATRA, however, is associated with the retinoic acid syndrome and relapse is also a problem. In relapsed patients, arsenic trioxide is considered the treatment of choice. Arsenic trioxide is a trivalent arsenical that selectively kills APL cells. To better understand how arsenic trioxide perturbs cellular functions we chose to screen a genome-wide set of Saccharomyces cerevisiae deletion strains for sensitivity or resistance to the drug. The idea was that genes whose loss conferred sensitivity to the drug would reflect mechanisms of cell death, while genes whose loss conferred resistance would suggest mechanisms of selectivity. 7.6% of the 4,564 mutants were more sensitive to arsenic trioxide than the wild-type strain, while 1.5% was more resistant. In accordance with published studies in mammalian cells, yeast mutants lacking genes required for cytoskeleton stability, response to oxidative stress and DNA repair were prominent in the sensitive list. The most prominent genes in the resistant list were that encoding the plasma membrane transporter, Fps1, Hog1 and repressors of Hog1. Fps1 is an aquaglyceroporin that mediates plasma membrane glycerol flux and uptake of inorganic arsenic in yeast. Its activity is controlled by the high osmolarity MAPK signalling or HOG pathway. There was a clear correlation between genes involved in modulating HOG pathway activity and altered arsenic trioxide tolerance in yeast. In mammalian cells, aquaglyceroporin 9 is the human homolog of yeast Fps1 and the p38 MAPK signalling cascade constitutes the analogous pathway to HOG. APL is characterized by chromosomal rearrangements of 17q21 leading to the formation of fusion proteins involving retinoic acid receptor α. Notably, the fusion protein interacts with p38 kinase and modulates its activity. Our findings imply that modulation of p38 by the APL fusion protein leads to increased arsenic trioxide uptake via aquaglyceroporin 9 in APL cells. This mechanism may account for the selectivity of arsenic trioxide for APL cells.

scholarly journals Confined diffusion of transmembrane proteins and lipids induced by the same actin meshwork lining the plasma membrane

2016 ◽  
Vol 27 (7) ◽  
pp. 1101-1119 ◽  
Author(s):  
Takahiro K. Fujiwara ◽  
Kokoro Iwasawa ◽  
Ziya Kalay ◽  
Taka A. Tsunoyama ◽  
Yusuke Watanabe ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Molecular Diffusion ◽  
Electron Tomography ◽  
Transmembrane Protein ◽  
Mesh Size ◽  
Domain Size ◽  
Membrane Skeleton ◽  
Reaction Rates ◽  
Single Particle Tracking ◽  
Major Mechanism

The mechanisms by which the diffusion rate in the plasma membrane (PM) is regulated remain unresolved, despite their importance in spatially regulating the reaction rates in the PM. Proposed models include entrapment in nanoscale noncontiguous domains found in PtK2 cells, slow diffusion due to crowding, and actin-induced compartmentalization. Here, by applying single-particle tracking at high time resolutions, mainly to the PtK2-cell PM, we found confined diffusion plus hop movements (termed “hop diffusion”) for both a nonraft phospholipid and a transmembrane protein, transferrin receptor, and equal compartment sizes for these two molecules in all five of the cell lines used here (actual sizes were cell dependent), even after treatment with actin-modulating drugs. The cross-section size and the cytoplasmic domain size both affected the hop frequency. Electron tomography identified the actin-based membrane skeleton (MSK) located within 8.8 nm from the PM cytoplasmic surface of PtK2 cells and demonstrated that the MSK mesh size was the same as the compartment size for PM molecular diffusion. The extracellular matrix and extracellular domains of membrane proteins were not involved in hop diffusion. These results support a model of anchored TM-protein pickets lining actin-based MSK as a major mechanism for regulating diffusion.

scholarly journals Atlas of ACE2 gene expression in mammals reveals novel insights in transmisson of SARS-Cov-2

2020 ◽  
Author(s):  
Kun Sun ◽  
Liuqi Gu ◽  
Li Ma ◽  
Yunfeng Duan
Keyword(s):  
Mammalian Cells ◽  
Clinical Symptoms ◽  
Close Contact ◽  
Transmembrane Protein ◽  
Mammalian Species ◽  
High Conservation ◽  
Novel Coronavirus ◽  
Species Specific ◽  
High Level ◽  
Ace2 Gene

AbstractBackgroundCOVID-19 has become a worldwide pandemic. It is caused by a novel coronavirus named SARS-CoV-2 with elusive origin. SARS-CoV-2 infects mammalian cells by binding to ACE2, a transmembrane protein. Therefore, the conservation of ACE2 and its expression pattern across mammalian species, which are yet to be comprehensively investigated, may provide valuable insights into tracing potential hosts of SARS-CoV-2.MethodsWe analyzed gene conservation of ACE2 across mammals and collected more than 140 transcriptome datasets from human and common mammalian species, including presumed hosts of SARS-CoV-2 and other animals in close contact with humans. In order to enable comparisons across species and tissues, we used a unified pipeline to quantify and normalize ACE2 expression levels.ResultsWe first found high conservation of ACE2 genes among common mammals at both DNA and peptide levels, suggesting that a broad range of mammalian species can potentially be the hosts of SARS-CoV-2. Next, we showed that high level of ACE2 expression in certain human tissues is consistent with clinical symptoms of COVID-19 patients. Furthermore, we observed that ACE2 expressed in a species-specific manner in the mammals examined. Notably, high expression in skin and eyes in cat and dog suggested that these animals may play roles in transmitting SARS-CoV-2 to humans.ConclusionsThrough building the first atlas of ACE2 expression in pets and livestock, we identified species and tissues susceptible to SARS-CoV-2 infection, yielding novel insights into the viral transmission.

scholarly journals Calmodulin-microtubule association in cultured mammalian cells.

1984 ◽  
Vol 98 (3) ◽  
pp. 904-910 ◽  
Author(s):  
W J Deery ◽  
A R Means ◽  
B R Brinkley
Keyword(s):  
Plasma Membrane ◽  
Mammalian Cells ◽  
Cell System ◽  
The Other ◽  
Microtubule Assembly ◽  
Cytoplasmic Microtubule ◽  
Hypotonic Treatment ◽  
Cytoplasmic Microtubules ◽  
Triton X ◽  
Ca Sensitivity

A Triton X-100-lysed cell system has been used to identify calmodulin on the cytoskeleton of 3T3 and transformed SV3T3 cells. By indirect immunofluorescence, calmodulin was found to be associated with both the cytoplasmic microtubule complex and the centrosomes. A number of cytoplasmic microtubules more resistant to disassembly upon either cold (0-4 degrees C) or hypotonic treatment, as well as following dilution have been identified. Most of the stable microtubules appeared to be associated with the centrosome at one end and with the plasma membrane at the other end. These microtubules could be induced to depolymerize, however, by micromolar Ca++ concentrations. These data suggest that, by interacting directly with the microtubule, calmodulin may influence microtubule assembly and ensure the Ca++-sensitivity of both mitotic and cytoplasmic microtubules.

scholarly journals Lateral diffusion of wild-type and mutant Ld antigens in L cells.

1984 ◽  
Vol 99 (6) ◽  
pp. 2333-2335 ◽  
Author(s):  
M Edidin ◽  
M Zuniga
Keyword(s):  
Plasma Membrane ◽  
Diffusion Coefficients ◽  
Transmembrane Protein ◽  
Transmembrane Proteins ◽  
Lateral Diffusion ◽  
Cytoplasmic Domain ◽  
Histocompatibility Antigen ◽  
Wild Type ◽  
Major Histocompatibility Antigen ◽  
Cytoplasmic Side

We have compared the lateral diffusion of intact transmembrane proteins, wild-type H-2Ld antigens, with that of mutants truncated in the cytoplasmic domain. Diffusion coefficients and mobile fractions were similar for all molecules examined, from wild-type Ld antigens with 31 residues on the cytoplasmic side of the plasma membrane to mutants with only four residues in the cytoplasmic domain. This result limits ways in which the lateral diffusion of a major histocompatibility antigen, a transmembrane protein, can be constrained by interactions with other molecules.

Sign in / Sign up

Export Citation Format

Share Document