Plasma membrane organization is essential for balancing competing pseudopod- and uropod-promoting signals during neutrophil polarization and migration.

Abstract:

:Exposure of neutrophils to chemoattractant induces cell polarization and migration. These behaviors require the asymmetric activation of distinct signaling pathways and cytoskeletal elements in the protruding pseudopod at the front of cells and the retracting uropod at the rear. An important outstanding question is, how does the organization of the plasma membrane participate in establishing asymmetry during polarization and migration? To answer this question, we investigated the function of cholesterol, a lipid known to influence membrane organization. Using controlled cholesterol depletion, we found that a cholesterol-dependent membrane organization enabled cell polarization and migration by promoting uropod function and suppressing ectopic pseudopod formation. At a mechanistic level, we showed that cholesterol was directly required for suppressing inappropriate activation of the pseudopod-promoting Gi/PI3-kinase signaling pathway. Furthermore, cholesterol was required for dampening Gi-dependent negative feedback on the RhoA signaling pathway, thus enabling RhoA activation and uropod function. Our findings suggest a model in which a cholesterol-dependent membrane organization plays an essential role in the establishment of cellular asymmetry by balancing the activation and segregating the localization of competing pseudopod- and uropod-inducing signaling pathways during neutrophil polarization and migration.

journal_name

Mol Biol Cell

authors

Bodin S,Welch MD

doi

10.1091/mbc.e05-04-0358

keywords:

subject

Has Abstract

pub_date

2005-12-01 00:00:00

pages

5773-83

issue

12

eissn

1059-1524

issn

1939-4586

pii

E05-04-0358

journal_volume

16

pub_type

杂志文章
  • Ribosome-binding proteins Mdm38 and Mba1 display overlapping functions for regulation of mitochondrial translation.

    abstract::Biogenesis of respiratory chain complexes depends on the expression of mitochondrial-encoded subunits. Their synthesis occurs on membrane-associated ribosomes and is probably coupled to their membrane insertion. Defects in expression of mitochondrial translation products are among the major causes of mitochondrial dis...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e10-02-0101

    authors: Bauerschmitt H,Mick DU,Deckers M,Vollmer C,Funes S,Kehrein K,Ott M,Rehling P,Herrmann JM

    更新日期:2010-06-15 00:00:00

  • The proteomics of quiescent and nonquiescent cell differentiation in yeast stationary-phase cultures.

    abstract::As yeast cultures enter stationary phase in rich, glucose-based medium, differentiation of two major subpopulations of cells, termed quiescent and nonquiescent, is observed. Differences in mRNA abundance between exponentially growing and stationary-phase cultures and quiescent and nonquiescent cells are known, but lit...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E10-06-0499

    authors: Davidson GS,Joe RM,Roy S,Meirelles O,Allen CP,Wilson MR,Tapia PH,Manzanilla EE,Dodson AE,Chakraborty S,Carter M,Young S,Edwards B,Sklar L,Werner-Washburne M

    更新日期:2011-04-01 00:00:00

  • Identification of integrin beta subunit mutations that alter heterodimer function in situ.

    abstract::We conducted a genetic screen for mutations in myospheroid, the gene encoding the Drosophila betaPS integrin subunit, and identified point mutants in all of the structural domains of the protein. Surprisingly, we find that mutations in very strongly conserved residues will often allow sufficient integrin function to s...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e04-02-0085

    authors: Jannuzi AL,Bunch TA,West RF,Brower DL

    更新日期:2004-08-01 00:00:00

  • Synthetic lethal interaction of the mitochondrial phosphatidylethanolamine biosynthetic machinery with the prohibitin complex of Saccharomyces cerevisiae.

    abstract::The majority of mitochondrial phosphatidylethanolamine (PtdEtn), a phospholipid essential for aerobic growth of yeast cells, is synthesized by phosphatidylserine decarboxylase 1 (Psd1p) in the inner mitochondrial membrane (IMM). To identify components that become essential when the level of mitochondrial PtdEtn is dec...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e02-05-0263

    authors: Birner R,Nebauer R,Schneiter R,Daum G

    更新日期:2003-02-01 00:00:00

  • Small heat shock proteins target mutant cystic fibrosis transmembrane conductance regulator for degradation via a small ubiquitin-like modifier-dependent pathway.

    abstract::Small heat shock proteins (sHsps) bind destabilized proteins during cell stress and disease, but their physiological functions are less clear. We evaluated the impact of Hsp27, an sHsp expressed in airway epithelial cells, on the common protein misfolding mutant that is responsible for most cystic fibrosis. F508del cy...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E12-09-0678

    authors: Ahner A,Gong X,Schmidt BZ,Peters KW,Rabeh WM,Thibodeau PH,Lukacs GL,Frizzell RA

    更新日期:2013-01-01 00:00:00

  • Dynamin GTPase domain mutants block endocytic vesicle formation at morphologically distinct stages.

    abstract::Abundant evidence has shown that the GTPase dynamin is required for receptor-mediated endocytosis, but its exact role in endocytic clathrin-coated vesicle formation remains to be established. Whereas dynamin GTPase domain mutants that are defective in GTP binding and hydrolysis are potent dominant-negative inhibitors ...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.12.9.2578

    authors: Damke H,Binns DD,Ueda H,Schmid SL,Baba T

    更新日期:2001-09-01 00:00:00

  • Rsp5 and Mdm30 reshape the mitochondrial network in response to age-induced vacuole stress.

    abstract::Mitochondrial decline is a hallmark of aging, and cells are equipped with many systems to regulate mitochondrial structure and function in response to stress and metabolic alterations. Here, using budding yeast, we identify a proteolytic pathway that contributes to alterations in mitochondrial structure in aged cells ...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E19-02-0094

    authors: Goodrum JM,Lever AR,Coody TK,Gottschling DE,Hughes AL

    更新日期:2019-08-01 00:00:00

  • Epidermal growth factor-induced contraction regulates paxillin phosphorylation to temporally separate traction generation from de-adhesion.

    abstract::Directed cell migration is mediated by cycles of protrusion, adhesion, traction generation on the extracellular matrix and retraction. However, how the events after protrusion are timed, and what dictates their temporal order is completely unknown. We used acute epidermal growth factor (EGF) stimulation of epidermal k...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e09-03-0219

    authors: Schneider IC,Hays CK,Waterman CM

    更新日期:2009-07-01 00:00:00

  • Leishmania donovani restricts mitochondrial dynamics to enhance miRNP stability and target RNA repression in host macrophages.

    abstract::MicroRNAs (miRNAs), the tiny regulatory RNAs, form complexes with Argonaute (Ago) proteins and inhibit gene expression in metazoan cells. While studying parasite-invaded macrophages, we identify a unique mode of gene regulation in which the parasite Leishmania donovani (Ld) causes mitochondrial depolarization, reduces...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E16-06-0388

    authors: Chakrabarty Y,Bhattacharyya SN

    更新日期:2017-07-15 00:00:00

  • Focal adhesion kinase protein regulates Wnt3a gene expression to control cell fate specification in the developing neural plate.

    abstract::Focal adhesion kinase (FAK) is a cytoplasmic tyrosine kinase protein localized to regions called focal adhesions, which are contact points between cells and the extracellular matrix. FAK protein acts as a scaffold to transfer adhesion-dependent and growth factor signals into the cell. Increased FAK expression is linke...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E10-12-0932

    authors: Fonar Y,Gutkovich YE,Root H,Malyarova A,Aamar E,Golubovskaya VM,Elias S,Elkouby YM,Frank D

    更新日期:2011-07-01 00:00:00

  • CD74 is a member of the regulated intramembrane proteolysis-processed protein family.

    abstract::Quite a few regulatory proteins, including transcription factors, are normally maintained in a dormant state to be activated after internal or environmental cues. Recently, a novel strategy, requiring proteolytic cleavage, was described for the mobilization of dormant transcription factors. These transcription factors...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e05-04-0327

    authors: Becker-Herman S,Arie G,Medvedovsky H,Kerem A,Shachar I

    更新日期:2005-11-01 00:00:00

  • E-cadherin adhesion activates c-Src signaling at cell-cell contacts.

    abstract::Cadherin-based cell-cell contacts are prominent sites for phosphotyrosine signaling, being enriched in tyrosine-phosphorylated proteins and tyrosine kinases and phosphatases. The functional interplay between cadherin adhesion and tyrosine kinase signaling, however, is complex and incompletely understood. In this repor...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e06-12-1154

    authors: McLachlan RW,Kraemer A,Helwani FM,Kovacs EM,Yap AS

    更新日期:2007-08-01 00:00:00

  • ATP-2 interacts with the PLAT domain of LOV-1 and is involved in Caenorhabditis elegans polycystin signaling.

    abstract::Caenorhabditis elegans is a powerful model to study the molecular basis of autosomal dominant polycystic kidney disease (ADPKD). ADPKD is caused by mutations in the polycystic kidney disease (PKD)1 or PKD2 gene, encoding polycystin (PC)-1 or PC-2, respectively. The C. elegans polycystins LOV-1 and PKD-2 are required f...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e04-09-0851

    authors: Hu J,Barr MM

    更新日期:2005-02-01 00:00:00

  • The role of HYAL2 in LSS-induced glycocalyx impairment and the PKA-mediated decrease in eNOS-Ser-633 phosphorylation and nitric oxide production.

    abstract::Hyaluronan (HA) in the endothelial glycocalyx serves as a mechanotransducer for high-shear-stress-stimulated endothelial nitric oxide synthase (eNOS) phosphorylation and nitric oxide (NO) production. Low shear stress (LSS) has been shown to contribute to endothelial inflammation and atherosclerosis by impairing the ba...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E16-04-0241

    authors: Kong X,Chen L,Ye P,Wang Z,Zhang J,Ye F,Chen S

    更新日期:2016-12-15 00:00:00

  • The septin-associated kinase Gin4 recruits Gps1 to the site of cell division.

    abstract::Cell cycle-dependent morphogenesis of unicellular organisms depends on the spatiotemporal control of cell polarity. Rho GTPases are the major players that guide cells through structural reorganizations such as cytokinesis (Rho1 dependent) and polarity establishment (Cdc42 dependent). In budding yeast, the protein Gps1...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E16-09-0687

    authors: Meitinger F,Pereira G

    更新日期:2017-04-01 00:00:00

  • Isolation and contraction of the stress fiber.

    abstract::Stress fibers were isolated from cultured human foreskin fibroblasts and bovine endothelial cells, and their contraction was demonstrated in vitro. Cells in culture dishes were first treated with a low-ionic-strength extraction solution and then further extracted using detergents. With gentle washes by pipetting, the ...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.9.7.1919

    authors: Katoh K,Kano Y,Masuda M,Onishi H,Fujiwara K

    更新日期:1998-07-01 00:00:00

  • Nuclear cathepsin F regulates activation markers in rat hepatic stellate cells.

    abstract::Activation of hepatic stellate cells during liver fibrosis is a major event facilitating an increase in extracellular matrix deposition. The up-regulation of smooth muscle alpha-actin and collagen type I is indicative of the activation process. The involvement of cysteine cathepsins, a class of lysosomal cysteine prot...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e08-03-0291

    authors: Maubach G,Lim MC,Zhuo L

    更新日期:2008-10-01 00:00:00

  • What makes the cell cycle tick? a celebration of the awesome power of biochemistry and the frog egg.

    abstract::The cell cycle, a 19th century discovery of cytologists, only achieved a satisfactory biochemical explanation in the last 20 years of the 20th century. This personal retrospective focuses on how biochemical studies of the frog egg helped identify the cyclin-based mitotic oscillator and how this approach quickly merged...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E20-10-0626

    authors: Kirschner M

    更新日期:2020-12-15 00:00:00

  • Fifty years of microtubule sliding in cilia.

    abstract::Motility of cilia (also known as flagella in some eukaryotes) is based on axonemal doublet microtubule sliding that is driven by the dynein molecular motors. Dyneins are organized into intricately patterned inner and outer rows of arms, whose collective activity is to produce inter-microtubule movement. However, to ge...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E17-07-0483

    authors: King SM,Sale WS

    更新日期:2018-03-15 00:00:00

  • CARMIL2 is a novel molecular connection between vimentin and actin essential for cell migration and invadopodia formation.

    abstract::Cancer cell migration requires the regulation of actin networks at protrusions associated with invadopodia and other leading edges. Carcinomas become invasive after undergoing an epithelial-mesenchymal transition characterized by the appearance of vimentin filaments. While vimentin expression correlates with cell migr...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E15-08-0552

    authors: Lanier MH,Kim T,Cooper JA

    更新日期:2015-12-15 00:00:00

  • Phosphatidylinositol 3,5-bisphosphate regulates the transition between trans-SNARE complex formation and vacuole membrane fusion.

    abstract::Phosphoinositides (PIs) regulate a myriad of cellular functions including membrane fusion, as exemplified by the yeast vacuole, which uses various PIs at different stages of fusion. In light of this, the effect of phosphatidylinositol 3,5-bisphosphate (PI(3,5)P2) on vacuole fusion remains unknown. PI(3,5)P2 is made by...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E18-08-0505

    authors: Miner GE,Sullivan KD,Guo A,Jones BC,Hurst LR,Ellis EC,Starr ML,Fratti RA

    更新日期:2019-01-15 00:00:00

  • Drosophila tubulin-binding cofactor B is required for microtubule network formation and for cell polarity.

    abstract::Microtubules (MTs) are essential for cell division, shape, intracellular transport, and polarity. MT stability is regulated by many factors, including MT-associated proteins and proteins controlling the amount of free tubulin heterodimers available for polymerization. Tubulin-binding cofactors are potential key regula...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E11-07-0633

    authors: Baffet AD,Benoit B,Januschke J,Audo J,Gourhand V,Roth S,Guichet A

    更新日期:2012-09-01 00:00:00

  • Overlapping roles of Drosophila Drak and Rok kinases in epithelial tissue morphogenesis.

    abstract::Dynamic regulation of cytoskeletal contractility through phosphorylation of the nonmuscle Myosin-II regulatory light chain (MRLC) provides an essential source of tension for shaping epithelial tissues. Rho GTPase and its effector kinase ROCK have been implicated in regulating MRLC phosphorylation in vivo, but evidence...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E10-04-0328

    authors: Neubueser D,Hipfner DR

    更新日期:2010-08-15 00:00:00

  • Intracellular transport, assembly, and degradation of wild-type and disease-linked mutant gap junction proteins.

    abstract::More than 130 different mutations in the gap junction integral plasma membrane protein connexin32 (Cx32) have been linked to the human peripheral neuropathy X-linked Charcot-Marie-Tooth disease (CMTX). How these various mutants are processed by the cell and the mechanism(s) by which they cause CMTX are unknown. To add...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.11.6.1933

    authors: VanSlyke JK,Deschenes SM,Musil LS

    更新日期:2000-06-01 00:00:00

  • A statistical anomaly indicates symbiotic origins of eukaryotic membranes.

    abstract::Compositional analyses of nucleic acids and proteins have shed light on possible origins of living cells. In this work, rigorous compositional analyses of ∼5000 plasma membrane lipid constituents of 273 species in the three life domains (archaea, eubacteria, and eukaryotes) revealed a remarkable statistical paradox, i...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E14-06-1078

    authors: Bansal S,Mittal A

    更新日期:2015-04-01 00:00:00

  • Adaptins: the final recount.

    abstract::Adaptins are subunits of adaptor protein (AP) complexes involved in the formation of intracellular transport vesicles and in the selection of cargo for incorporation into the vesicles. In this article, we report the results of a survey for adaptins from sequenced genomes including those of man, mouse, the fruit fly Dr...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.12.10.2907

    authors: Boehm M,Bonifacino JS

    更新日期:2001-10-01 00:00:00

  • Inhibiting endoplasmic reticulum (ER)-associated degradation of misfolded Yor1p does not permit ER export despite the presence of a diacidic sorting signal.

    abstract::Capture of newly synthesized proteins into endoplasmic reticulum (ER)-derived coat protomer type II (COPII) vesicles represents a critical juncture in the quality control of protein biogenesis within the secretory pathway. The yeast ATP-binding cassette transporter Yor1p is a pleiotropic drug pump that shows homology ...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e07-01-0046

    authors: Pagant S,Kung L,Dorrington M,Lee MC,Miller EA

    更新日期:2007-09-01 00:00:00

  • Regulation of NADPH oxidase activity by Rac GTPase activating protein(s).

    abstract::Activation of the NADPH oxidase of phagocytic cells requires the action of Rac2 or Rac1, members of the Ras superfamily of GTP-binding proteins. Rac proteins are active when in the GTP-bound form and can be regulated by a variety of proteins that modulate the exchange of GDP for GTP and/or GTP hydrolysis. The p190 Rac...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.4.11.1217

    authors: Heyworth PG,Knaus UG,Settleman J,Curnutte JT,Bokoch GM

    更新日期:1993-11-01 00:00:00

  • Many roads to symmetry breaking: molecular mechanisms and theoretical models of yeast cell polarity.

    abstract::Mathematical modeling has been instrumental in identifying common principles of cell polarity across diverse systems. These principles include positive feedback loops that are required to destabilize a spatially uniform state of the cell. The conserved small G-protein Cdc42 is a master regulator of eukaryotic cellular...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章,评审

    doi:10.1091/mbc.E16-10-0739

    authors: Goryachev AB,Leda M

    更新日期:2017-02-01 00:00:00

  • TRAF2 phosphorylation promotes NF-κB-dependent gene expression and inhibits oxidative stress-induced cell death.

    abstract::Tumor necrosis factor α (TNF-α) receptor-associated factor 2 (TRAF2) regulates activation of the c-Jun N-terminal kinase (JNK)/c-Jun and the inhibitor of κB kinase (IKK)/nuclear factor κB (NF-κB) signaling cascades in response to TNF-α stimulation. Gene knockout studies have revealed that TRAF2 inhibits TNF-α-induced ...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E10-06-0556

    authors: Zhang L,Blackwell K,Altaeva A,Shi Z,Habelhah H

    更新日期:2011-01-01 00:00:00