Regulation of macropinocytosis by p21-activated kinase-1.

Abstract:

:The process of macropinocytosis is an essential aspect of normal cell function, contributing to both growth and motile processes of cells. p21-activated kinases (PAKs) are targets for activated Rac and Cdc42 guanosine 5'-triphosphatases and have been shown to regulate the actin-myosin cytoskeleton. In fibroblasts PAK1 localizes to areas of membrane ruffling, as well as to amiloride-sensitive pinocytic vesicles. Expression of a PAK1 kinase autoinhibitory domain blocked both platelet-derived growth factor- and RacQ61L-stimulated uptake of 70-kDa dextran particles, whereas an inactive version of this domain did not, indicating that PAK kinase activity is required for normal growth factor-induced macropinocytosis. The mechanisms by which PAK modulate macropinocytosis were examined in NIH3T3 cell lines expressing various PAK1 constructs under the control of a tetracycline-responsive transactivator. Cells expressing PAK1 (H83,86L), a mutant that dramatically stimulates formation of dorsal membrane ruffles, exhibited increased macropinocytic uptake of 70-kDa dextran particles in the absence of additional stimulation. This effect was not antagonized by coexpression of dominant-negative Rac1-T17N. In the presence of platelet-derived growth factor, both PAK1 (H83,86L) and a highly kinase active PAK1 (T423E) mutant dramatically enhanced the uptake of 70-kDa dextran. Neither wild-type PAK1 nor vector controls exhibited enhanced macropinocytosis, nor did PAK1 (H83,86L) affect clathrin-dependent endocytic mechanisms. Active versions of PAK1 enhanced both growth factor-stimulated 70-kDa dextran uptake and efflux, suggesting that PAK1 activity modulated pinocytic vesicle cycling. These data indicate that PAK1 plays an important regulatory role in the process of macropinocytosis, perhaps related to the requirement for PAK in directed cell motility.

journal_name

Mol Biol Cell

authors

Dharmawardhane S,Schürmann A,Sells MA,Chernoff J,Schmid SL,Bokoch GM

doi

10.1091/mbc.11.10.3341

keywords:

subject

Has Abstract

pub_date

2000-10-01 00:00:00

pages

3341-52

issue

10

eissn

1059-1524

issn

1939-4586

journal_volume

11

pub_type

杂志文章
  • The near demise and subsequent revival of classical genetics for investigating Caenorhabditis elegans embryogenesis: RNAi meets next-generation DNA sequencing.

    abstract::Molecular genetic investigation of the early Caenorhabditis elegans embryo has contributed substantially to the discovery and general understanding of the genes, pathways, and mechanisms that regulate and execute developmental and cell biological processes. Initially, worm geneticists relied exclusively on a classical...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E11-03-0185

    authors: Bowerman B

    更新日期:2011-10-01 00:00:00

  • Nup93, a vertebrate homologue of yeast Nic96p, forms a complex with a novel 205-kDa protein and is required for correct nuclear pore assembly.

    abstract::Yeast and vertebrate nuclear pores display significant morphological similarity by electron microscopy, but sequence similarity between the respective proteins has been more difficult to observe. Herein we have identified a vertebrate nucleoporin, Nup93, in both human and Xenopus that has proved to be an evolutionaril...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.8.10.2017

    authors: Grandi P,Dang T,Pané N,Shevchenko A,Mann M,Forbes D,Hurt E

    更新日期:1997-10-01 00:00:00

  • Reorganization of actin cytoskeleton by the phosphoinositide metabolite glycerophosphoinositol 4-phosphate.

    abstract::Glycerophosphoinositol 4-phosphate (GroPIns-4P) is a biologically active, water-soluble phospholipase A metabolite derived from phosphatidylinositol 4-phosphate, whose cellular concentrations have been reported to increase in Ras-transformed cells. It is therefore important to understand its biological activities. Her...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e02-04-0179

    authors: Mancini R,Piccolo E,Mariggio' S,Filippi BM,Iurisci C,Pertile P,Berrie CP,Corda D

    更新日期:2003-02-01 00:00:00

  • Association of ARVCF with zonula occludens (ZO)-1 and ZO-2: binding to PDZ-domain proteins and cell-cell adhesion regulate plasma membrane and nuclear localization of ARVCF.

    abstract::ARVCF, an armadillo-repeat protein of the p120(ctn) family, associates with classical cadherins and is present in adherens junctions, but its function is poorly understood. Here, we show that ARVCF interacts via a C-terminal PDZ-binding motif with zonula occludens (ZO)-1 and ZO-2. ARVCF and ZO-1 partially colocalize i...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e04-04-0350

    authors: Kausalya PJ,Phua DC,Hunziker W

    更新日期:2004-12-01 00:00:00

  • Protein targeting of an unusual, evolutionarily conserved adenylate kinase to a eukaryotic flagellum.

    abstract::The eukaryotic flagellum is a large structure into which specific constituent proteins must be targeted, transported and assembled after their synthesis in the cytoplasm. Using Trypanosoma brucei and a proteomic approach, we have identified and characterized a novel set of adenylate kinase proteins that are localized ...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e04-03-0217

    authors: Pullen TJ,Ginger ML,Gaskell SJ,Gull K

    更新日期:2004-07-01 00:00:00

  • Revised subunit order of mammalian septin complexes explains their in vitro polymerization properties.

    abstract::Septins are conserved GTP-binding cytoskeletal proteins that polymerize into filaments by end-to-end joining of hetero-oligomeric complexes. In human cells, both hexamers and octamers exist, and crystallography studies predicted the order of the hexamers to be SEPT7-SEPT6-SEPT2-SEPT2-SEPT6-SEPT7, while octamers are th...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E20-06-0398

    authors: Soroor F,Kim MS,Palander O,Balachandran Y,Collins RF,Benlekbir S,Rubinstein JL,Trimble WS

    更新日期:2021-02-01 00:00:00

  • The relationship between metastatic potential and in vitro mechanical properties of osteosarcoma cells.

    abstract::Osteosarcoma is the most frequent primary tumor of bone and is characterized by its high tendency to metastasize in lungs. Although treatment in cases of early diagnosis results in a 5-yr survival rate of nearly 60%, the prognosis for patients with secondary lesions at diagnosis is poor, and their 5-yr survival rate r...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E18-08-0545

    authors: Holenstein CN,Horvath A,Schär B,Schoenenberger AD,Bollhalder M,Goedecke N,Bartalena G,Otto O,Herbig M,Guck J,Müller DA,Snedeker JG,Silvan U

    更新日期:2019-03-21 00:00:00

  • Arp2/3 complex is important for filopodia formation, growth cone motility, and neuritogenesis in neuronal cells.

    abstract::A role of Arp2/3 complex in lamellipodia is well established, whereas its roles in filopodia formation remain obscure. We addressed this question in neuronal cells, in which motility is heavily based on filopodia, and we found that Arp2/3 complex is involved in generation of both lamellipodia and filopodia in growth c...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e07-09-0964

    authors: Korobova F,Svitkina T

    更新日期:2008-04-01 00:00:00

  • Histone deacetylase inhibitors trigger a G2 checkpoint in normal cells that is defective in tumor cells.

    abstract::Important aspects of cell cycle regulation are the checkpoints, which respond to a variety of cellular stresses to inhibit cell cycle progression and act as protective mechanisms to ensure genomic integrity. An increasing number of tumor suppressors are being demonstrated to have roles in checkpoint mechanisms, implyi...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.11.6.2069

    authors: Qiu L,Burgess A,Fairlie DP,Leonard H,Parsons PG,Gabrielli BG

    更新日期:2000-06-01 00:00:00

  • gdt1, a new signal transduction component for negative regulation of the growth-differentiation transition in Dictyostelium discoideum.

    abstract::Discoidin I expression was used as a marker to screen for mutants affected in the growth-differentiation transition (GDT) of Dictyostelium. By REMI mutagenesis we have isolated mutant 2-9, an overexpressor of discoidin I. It displays normal morphogenesis but shows premature entry into the developmental cycle. The disr...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.11.5.1631

    authors: Zeng C,Anjard C,Riemann K,Konzok A,Nellen W

    更新日期:2000-05-01 00:00:00

  • Early stages of the secretory pathway, but not endosomes, are required for Cvt vesicle and autophagosome assembly in Saccharomyces cerevisiae.

    abstract::The Cvt pathway is a biosynthetic transport route for a distinct subset of resident yeast vacuolar hydrolases, whereas macroautophagy is a nonspecific degradative mechanism that allows cell survival during starvation. Yet, these two vacuolar trafficking pathways share a number of identical molecular components and are...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e03-07-0479

    authors: Reggiori F,Wang CW,Nair U,Shintani T,Abeliovich H,Klionsky DJ

    更新日期:2004-05-01 00:00:00

  • The double trouble of metabolic diseases: the diabetes-cancer link.

    abstract::The recent recognition of the clinical association between type 2 diabetes (T2D) and several types of human cancer has been further highlighted by reports of antidiabetic drugs treating or promoting cancer. At the cellular level, a plethora of molecules operating within distinct signaling pathways suggests cross-talk ...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E14-11-1550

    authors: Tudzarova S,Osman MA

    更新日期:2015-09-15 00:00:00

  • Novel genetic tools reveal Cdk5's major role in Golgi fragmentation in Alzheimer's disease.

    abstract::Golgi fragmentation is a common feature in multiple neurodegenerative diseases; however, the precise mechanism that causes fragmentation remains obscure. A potential link between Cdk5 and Golgi fragmentation in Alzheimer's disease (AD) was investigated in this study. Because Golgi is physiologically fragmented during ...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e07-11-1106

    authors: Sun KH,de Pablo Y,Vincent F,Johnson EO,Chavers AK,Shah K

    更新日期:2008-07-01 00:00:00

  • p27Kip1 acts downstream of N-cadherin-mediated cell adhesion to promote myogenesis beyond cell cycle regulation.

    abstract::It is widely acknowledged that cultured myoblasts can not differentiate at very low density. Here we analyzed the mechanism through which cell density influences myogenic differentiation in vitro. By comparing the behavior of C2C12 myoblasts at opposite cell densities, we found that, when cells are sparse, failure to ...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e04-07-0612

    authors: Messina G,Blasi C,La Rocca SA,Pompili M,Calconi A,Grossi M

    更新日期:2005-03-01 00:00:00

  • Reorganization of budding yeast cytoplasm upon energy depletion.

    abstract::Yeast cells, when exposed to stress, can enter a protective state in which cell division, growth, and metabolism are down-regulated. They remain viable in this state until nutrients become available again. How cells enter this protective survival state and what happens at a cellular and subcellular level are largely u...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E20-02-0125

    authors: Marini G,Nüske E,Leng W,Alberti S,Pigino G

    更新日期:2020-06-01 00:00:00

  • Regulation of sodium channel activity by capping of actin filaments.

    abstract::Ion transport in various tissues can be regulated by the cortical actin cytoskeleton. Specifically, involvement of actin dynamics in the regulation of nonvoltage-gated sodium channels has been shown. Herein, inside-out patch clamp experiments were performed to study the effect of the heterodimeric actin capping protei...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e02-09-0622

    authors: Shumilina EV,Negulyaev YA,Morachevskaya EA,Hinssen H,Khaitlina SY

    更新日期:2003-04-01 00:00:00

  • Changes in organization of the endoplasmic reticulum during Xenopus oocyte maturation and activation.

    abstract::The organization of the endoplasmic reticulum (ER) in the cortex of Xenopus oocytes was investigated during maturation and activation using a green fluorescent protein chimera, immunofluorescence, and electron microscopy. Dense clusters of ER developed on the vegetal side (the side opposite the meiotic spindle) during...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.12.4.1103

    authors: Terasaki M,Runft LL,Hand AR

    更新日期:2001-04-01 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

  • Cooperative assembly of CYK-4/MgcRacGAP and ZEN-4/MKLP1 to form the centralspindlin complex.

    abstract::Cytokinesis in metazoan cells requires a set of antiparallel microtubules that become bundled upon anaphase onset to form a structure known as the central spindle. Bundling of these microtubules requires a protein complex, centralspindlin, that consists of the CYK-4/MgcRacGAP Rho-family GTPase-activating protein and t...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e07-05-0468

    authors: Pavicic-Kaltenbrunner V,Mishima M,Glotzer M

    更新日期:2007-12-01 00:00:00

  • Altered levels of the Drosophila HRB87F/hrp36 hnRNP protein have limited effects on alternative splicing in vivo.

    abstract::The Drosophila melanogaster genes Hrb87F and Hrb98DE encode the fly proteins HRB87F and HRB98DE (also known as hrp36 and hrp38, respectively) that are most similar in sequence and function to mammalian A/B-type hnRNP proteins. Using overexpression and deletion mutants of Hrb87F, we have tested the hypothesis that the ...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.7.7.1059

    authors: Zu K,Sikes ML,Haynes SR,Beyer AL

    更新日期:1996-07-01 00:00:00

  • Dynein light intermediate chain: an essential subunit that contributes to spindle checkpoint inactivation.

    abstract::The dynein light intermediate chain (LIC) is a subunit unique to the cytoplasmic form of dynein, but how it contributes to dynein function is not fully understood. Previous work has established that the LIC homodimer binds directly to the dynein heavy chain and may mediate the attachment of dynein to centrosomes and o...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e08-05-0483

    authors: Mische S,He Y,Ma L,Li M,Serr M,Hays TS

    更新日期:2008-11-01 00:00:00

  • Characterizing the roles of Met31 and Met32 in coordinating Met4-activated transcription in the absence of Met30.

    abstract::Yeast sulfur metabolism is transcriptionally regulated by the activator Met4. Met4 lacks DNA-binding ability and relies on interactions with Met31 and Met32, paralogous proteins that bind the same cis-regulatory element, to activate its targets. Although Met31 and Met32 are redundant for growth in the absence of methi...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E11-06-0532

    authors: Carrillo E,Ben-Ari G,Wildenhain J,Tyers M,Grammentz D,Lee TA

    更新日期:2012-05-01 00:00:00

  • P38 mitogen-activated protein kinase activity is required during mitosis for timely satisfaction of the mitotic checkpoint but not for the fidelity of chromosome segregation.

    abstract::Although p38 activity is reported to be required as cells enter mitosis for proper spindle assembly and checkpoint function, its role during the division process remains controversial in lieu of direct data. We therefore conducted live cell studies to determine the effect on mitosis of inhibiting or depleting p38. We ...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e10-02-0125

    authors: Lee K,Kenny AE,Rieder CL

    更新日期:2010-07-01 00:00:00

  • An effector domain mutant of Arf6 implicates phospholipase D in endosomal membrane recycling.

    abstract::In this study, we investigated the role of phospholipase D (PLD) in mediating Arf6 function in cells. Expression of Arf6 mutants that are defective in activating PLD, Arf6N48R and Arf6N48I, inhibited membrane recycling to the plasma membrane (PM), resulting in an accumulation of tubular endosomal membranes. Additional...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e05-06-0523

    authors: Jovanovic OA,Brown FD,Donaldson JG

    更新日期:2006-01-01 00:00:00

  • The HOPS complex mediates autophagosome-lysosome fusion through interaction with syntaxin 17.

    abstract::Membrane fusion is generally controlled by Rabs, soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs), and tethering complexes. Syntaxin 17 (STX17) was recently identified as the autophagosomal SNARE required for autophagosome-lysosome fusion in mammals and Drosophila. In this study, to bett...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E13-08-0447

    authors: Jiang P,Nishimura T,Sakamaki Y,Itakura E,Hatta T,Natsume T,Mizushima N

    更新日期:2014-04-01 00:00:00

  • Receptor-mediated cell mechanosensing.

    abstract::Mechanosensing describes the ability of a cell to sense mechanical cues of its microenvironment, including not only all components of force, stress, and strain but also substrate rigidity, topology, and adhesiveness. This ability is crucial for the cell to respond to the surrounding mechanical cues and adapt to the ch...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章,评审

    doi:10.1091/mbc.E17-04-0228

    authors: Chen Y,Ju L,Rushdi M,Ge C,Zhu C

    更新日期:2017-11-07 00:00:00

  • RSBP-1 is a membrane-targeting subunit required by the Galpha(q)-specific but not the Galpha(o)-specific R7 regulator of G protein signaling in Caenorhabditis elegans.

    abstract::Regulator of G protein signaling (RGS) proteins inhibit G protein signaling by activating Galpha GTPase activity, but the mechanisms that regulate RGS activity are not well understood. The mammalian R7 binding protein (R7BP) can interact with all members of the R7 family of RGS proteins, and palmitoylation of R7BP can...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e09-07-0642

    authors: Porter MY,Koelle MR

    更新日期:2010-01-15 00:00:00

  • The HOG pathway dictates the short-term translational response after hyperosmotic shock.

    abstract::Cellular responses to environmental changes occur on different levels. We investigated the translational response of yeast cells after mild hyperosmotic shock by isolating mRNA associated with multiple ribosomes (polysomes) followed by array analysis. Globally, recruitment of preexisting mRNAs to ribosomes (translatio...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E10-01-0006

    authors: Warringer J,Hult M,Regot S,Posas F,Sunnerhagen P

    更新日期:2010-09-01 00:00:00

  • A myopathy-linked desmin mutation perturbs striated muscle actin filament architecture.

    abstract::Desmin interacts with nebulin establishing a direct link between the intermediate filament network and sarcomeres at the Z-discs. Here, we examined a desmin mutation, E245D, that is located within the coil IB (nebulin-binding) region of desmin and that has been reported to cause human cardiomyopathy and skeletal muscl...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e08-07-0753

    authors: Conover GM,Henderson SN,Gregorio CC

    更新日期:2009-02-01 00:00:00

  • Full-length dimeric MCAK is a more efficient microtubule depolymerase than minimal domain monomeric MCAK.

    abstract::MCAK belongs to the Kinesin-13 family, whose members depolymerize microtubules rather than translocate along them. We defined the minimal functional unit of MCAK as the catalytic domain plus the class specific neck (MD-MCAK), which is consistent with previous reports. We used steady-state ATPase kinetics, microtubule ...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e05-08-0821

    authors: Hertzer KM,Ems-McClung SC,Kline-Smith SL,Lipkin TG,Gilbert SP,Walczak CE

    更新日期:2006-02-01 00:00:00