Regulation of small GTPases by GEFs, GAPs, and GDIs.

Abstract:

:Small GTPases use GDP/GTP alternation to actuate a variety of functional switches that are pivotal for cell dynamics. The GTPase switch is turned on by GEFs, which stimulate dissociation of the tightly bound GDP, and turned off by GAPs, which accelerate the intrinsically sluggish hydrolysis of GTP. For Ras, Rho, and Rab GTPases, this switch incorporates a membrane/cytosol alternation regulated by GDIs and GDI-like proteins. The structures and core mechanisms of representative members of small GTPase regulators from most families have now been elucidated, illuminating their general traits combined with scores of unique features. Recent studies reveal that small GTPase regulators have themselves unexpectedly sophisticated regulatory mechanisms, by which they process cellular signals and build up specific cell responses. These mechanisms include multilayered autoinhibition with stepwise release, feedback loops mediated by the activated GTPase, feed-forward signaling flow between regulators and effectors, and a phosphorylation code for RhoGDIs. The flipside of these highly integrated functions is that they make small GTPase regulators susceptible to biochemical abnormalities that are directly correlated with diseases, notably a striking number of missense mutations in congenital diseases, and susceptible to bacterial mimics of GEFs, GAPs, and GDIs that take command of small GTPases in infections. This review presents an overview of the current knowledge of these many facets of small GTPase regulation.

journal_name

Physiol Rev

journal_title

Physiological reviews

authors

Cherfils J,Zeghouf M

doi

10.1152/physrev.00003.2012

subject

Has Abstract

pub_date

2013-01-01 00:00:00

pages

269-309

issue

1

eissn

0031-9333

issn

1522-1210

pii

93/1/269

journal_volume

93

pub_type

杂志文章,评审
  • Properties and regulation of the minK potassium channel protein.

    abstract::The minK gene encodes a protein of 130 amino acids that has a single transmembrane segment and is expressed in many tissues including heart, uterus, and kidney. When Xenopus oocytes are injected with minK mRNA, a very slowly activating voltage-dependent potassium current is induced in these cells. The induced channels...

    journal_title:Physiological reviews

    pub_type: 杂志文章,评审

    doi:10.1152/physrev.1997.77.3.627

    authors: Kaczmarek LK,Blumenthal EM

    更新日期:1997-07-01 00:00:00

  • Mechanisms of cancer cachexia.

    abstract::Up to 50% of cancer patients suffer from a progressive atrophy of adipose tissue and skeletal muscle, called cachexia, resulting in weight loss, a reduced quality of life, and a shortened survival time. Anorexia often accompanies cachexia, but appears not to be responsible for the tissue loss, particularly lean body m...

    journal_title:Physiological reviews

    pub_type: 杂志文章,评审

    doi:10.1152/physrev.00016.2008

    authors: Tisdale MJ

    更新日期:2009-04-01 00:00:00

  • Mechanisms Regulating Neuromuscular Junction Development and Function and Causes of Muscle Wasting.

    abstract::The neuromuscular junction is the chemical synapse between motor neurons and skeletal muscle fibers. It is designed to reliably convert the action potential from the presynaptic motor neuron into the contraction of the postsynaptic muscle fiber. Diseases that affect the neuromuscular junction may cause failure of this...

    journal_title:Physiological reviews

    pub_type: 杂志文章,评审

    doi:10.1152/physrev.00033.2014

    authors: Tintignac LA,Brenner HR,Rüegg MA

    更新日期:2015-07-01 00:00:00

  • Fluorescent proteins and their applications in imaging living cells and tissues.

    abstract::Green fluorescent protein (GFP) from the jellyfish Aequorea victoria and its homologs from diverse marine animals are widely used as universal genetically encoded fluorescent labels. Many laboratories have focused their efforts on identification and development of fluorescent proteins with novel characteristics and en...

    journal_title:Physiological reviews

    pub_type: 杂志文章,评审

    doi:10.1152/physrev.00038.2009

    authors: Chudakov DM,Matz MV,Lukyanov S,Lukyanov KA

    更新日期:2010-07-01 00:00:00

  • Transmembrane transport of endo- and xenobiotics by mammalian ATP-binding cassette multidrug resistance proteins.

    abstract::Multidrug Resistance Proteins (MRPs), together with the cystic fibrosis conductance regulator (CFTR/ABCC7) and the sulfonylurea receptors (SUR1/ABCC8 and SUR2/ABCC9) comprise the 13 members of the human "C" branch of the ATP binding cassette (ABC) superfamily. All C branch proteins share conserved structural features ...

    journal_title:Physiological reviews

    pub_type: 杂志文章,评审

    doi:10.1152/physrev.00035.2005

    authors: Deeley RG,Westlake C,Cole SP

    更新日期:2006-07-01 00:00:00

  • Endothelial Cell Metabolism.

    abstract::Endothelial cells (ECs) are more than inert blood vessel lining material. Instead, they are active players in the formation of new blood vessels (angiogenesis) both in health and (life-threatening) diseases. Recently, a new concept arose by which EC metabolism drives angiogenesis in parallel to well-established angiog...

    journal_title:Physiological reviews

    pub_type: 杂志文章,评审

    doi:10.1152/physrev.00001.2017

    authors: Eelen G,de Zeeuw P,Treps L,Harjes U,Wong BW,Carmeliet P

    更新日期:2018-01-01 00:00:00

  • Mammalian G proteins and their cell type specific functions.

    abstract::Heterotrimeric G proteins are key players in transmembrane signaling by coupling a huge variety of receptors to channel proteins, enzymes, and other effector molecules. Multiple subforms of G proteins together with receptors, effectors, and various regulatory proteins represent the components of a highly versatile sig...

    journal_title:Physiological reviews

    pub_type: 杂志文章,评审

    doi:10.1152/physrev.00003.2005

    authors: Wettschureck N,Offermanns S

    更新日期:2005-10-01 00:00:00

  • Expression and function of laminins in the embryonic and mature vasculature.

    abstract::Endothelial cells of the blood and lymphatic vasculature are polarized cells with luminal surfaces specialized to interact with inflammatory cells upon the appropriate stimulation; they contain specialized transcellular transport systems, and their basal surfaces are attached to an extracellular basement membrane. In ...

    journal_title:Physiological reviews

    pub_type: 杂志文章,评审

    doi:10.1152/physrev.00014.2004

    authors: Hallmann R,Horn N,Selg M,Wendler O,Pausch F,Sorokin LM

    更新日期:2005-07-01 00:00:00

  • Cellular and synaptic adaptations mediating opioid dependence.

    abstract::Although opioids are highly effective for the treatment of pain, they are also known to be intensely addictive. There has been a massive research investment in the development of opioid analgesics, resulting in a plethora of compounds with varying affinity and efficacy at all the known opioid receptor subtypes. Althou...

    journal_title:Physiological reviews

    pub_type: 杂志文章,评审

    doi:10.1152/physrev.2001.81.1.299

    authors: Williams JT,Christie MJ,Manzoni O

    更新日期:2001-01-01 00:00:00

  • Immunity, Hypoxia, and Metabolism-the Ménage à Trois of Cancer: Implications for Immunotherapy.

    abstract::It is generally accepted that metabolism is able to shape the immune response. Only recently we are gaining awareness that the metabolic crosstalk between different tumor compartments strongly contributes to the harsh tumor microenvironment (TME) and ultimately impairs immune cell fitness and effector functions. The m...

    journal_title:Physiological reviews

    pub_type: 杂志文章,评审

    doi:10.1152/physrev.00018.2019

    authors: Riera-Domingo C,Audigé A,Granja S,Cheng WC,Ho PC,Baltazar F,Stockmann C,Mazzone M

    更新日期:2020-01-01 00:00:00

  • Endocytosis, intracellular transport, and cytotoxic action of Shiga toxin and ricin.

    abstract::Protein toxins such as ricin and Shiga toxin with intracellular targets have to be endocytosed and translocated to the cytosol to inhibit the protein synthesis and thereby kill the cell. Ricin is internalized by both clathrin-dependent and -independent endocytic mechanisms, whereas Shiga toxin seems to be taken up exc...

    journal_title:Physiological reviews

    pub_type: 杂志文章,评审

    doi:10.1152/physrev.1996.76.4.949

    authors: Sandvig K,van Deurs B

    更新日期:1996-10-01 00:00:00

  • Cellular calcium transport in renal epithelia: measurement, mechanisms, and regulation.

    abstract::The kidneys play a vital role in mineral homeostasis. In this review, the handling of calcium and the methods currently applied to measuring its intracellular concentration are discussed. The bulk of calcium absorption proceeds in proximal tubules, with smaller fractions recovered by thick ascending limbs, distal conv...

    journal_title:Physiological reviews

    pub_type: 杂志文章,评审

    doi:10.1152/physrev.1995.75.3.429

    authors: Friedman PA,Gesek FA

    更新日期:1995-07-01 00:00:00

  • The new biology of gastrointestinal hormones.

    abstract::The classic concept of gastrointestinal endocrinology is that of a few peptides released to the circulation from endocrine cells, which are interspersed among other mucosal cells in the upper gastrointestinal tract. Today more than 30 peptide hormone genes are known to be expressed throughout the digestive tract, whic...

    journal_title:Physiological reviews

    pub_type: 杂志文章,评审

    doi:10.1152/physrev.1998.78.4.1087

    authors: Rehfeld JF

    更新日期:1998-10-01 00:00:00

  • Store-operated calcium channels.

    abstract::In electrically nonexcitable cells, Ca(2+) influx is essential for regulating a host of kinetically distinct processes involving exocytosis, enzyme control, gene regulation, cell growth and proliferation, and apoptosis. The major Ca(2+) entry pathway in these cells is the store-operated one, in which the emptying of i...

    journal_title:Physiological reviews

    pub_type: 杂志文章,评审

    doi:10.1152/physrev.00057.2003

    authors: Parekh AB,Putney JW Jr

    更新日期:2005-04-01 00:00:00

  • Peptide hormone regulation of angiogenesis.

    abstract::It is now apparent that regulation of blood vessel growth contributes to the classical actions of hormones on development, growth, and reproduction. Endothelial cells are ideally positioned to respond to hormones, which act in concert with locally produced chemical mediators to regulate their growth, motility, functio...

    journal_title:Physiological reviews

    pub_type: 杂志文章,评审

    doi:10.1152/physrev.00024.2009

    authors: Clapp C,Thebault S,Jeziorski MC,Martínez De La Escalera G

    更新日期:2009-10-01 00:00:00

  • The Arp2/3 Regulatory System and Its Deregulation in Cancer.

    abstract::The Arp2/3 complex is an evolutionary conserved molecular machine that generates branched actin networks. When activated, the Arp2/3 complex contributes the actin branched junction and thus cross-links the polymerizing actin filaments in a network that exerts a pushing force. The different activators initiate branched...

    journal_title:Physiological reviews

    pub_type: 杂志文章,评审

    doi:10.1152/physrev.00006.2017

    authors: Molinie N,Gautreau A

    更新日期:2018-01-01 00:00:00

  • Urothelial signaling.

    abstract::The urothelium, which lines the inner surface of the renal pelvis, the ureters, and the urinary bladder, not only forms a high-resistance barrier to ion, solute and water flux, and pathogens, but also functions as an integral part of a sensory web which receives, amplifies, and transmits information about its external...

    journal_title:Physiological reviews

    pub_type: 杂志文章,评审

    doi:10.1152/physrev.00030.2012

    authors: Birder L,Andersson KE

    更新日期:2013-04-01 00:00:00

  • Cyclic nucleotide phosphodiesterases: functional implications of multiple isoforms.

    abstract::In the last few years there has been a veritable explosion of knowledge about cyclic nucleotide phosphodiesterases. In particular, the accumulating data showing that there are a large number of different phosphodiesterase isozymes have triggered an equally large increase in interest about these enzymes. At least seven...

    journal_title:Physiological reviews

    pub_type: 杂志文章,评审

    doi:10.1152/physrev.1995.75.4.725

    authors: Beavo JA

    更新日期:1995-10-01 00:00:00

  • Beyond neurons: evidence that immune and glial cells contribute to pathological pain states.

    abstract::Chronic pain can occur after peripheral nerve injury, infection, or inflammation. Under such neuropathic pain conditions, sensory processing in the affected body region becomes grossly abnormal. Despite decades of research, currently available drugs largely fail to control such pain. This review explores the possibili...

    journal_title:Physiological reviews

    pub_type: 杂志文章,评审

    doi:10.1152/physrev.00011.2002

    authors: Watkins LR,Maier SF

    更新日期:2002-10-01 00:00:00

  • Dendritic cells: immune regulators in health and disease.

    abstract::Dendritic cells (DCs) are bone marrow-derived cells of both lymphoid and myeloid stem cell origin that populate all lymphoid organs including the thymus, spleen, and lymph nodes, as well as nearly all nonlymphoid tissues and organs. Although DCs are a moderately diverse set of cells, they all have potent antigen-prese...

    journal_title:Physiological reviews

    pub_type: 杂志文章,评审

    doi:10.1152/physrev.00023.2001

    authors: Lipscomb MF,Masten BJ

    更新日期:2002-01-01 00:00:00

  • Nonvertebrate hemoglobins: functions and molecular adaptations.

    abstract::Hemoglobin (Hb) occurs in all the kingdoms of living organisms. Its distribution is episodic among the nonvertebrate groups in contrast to vertebrates. Nonvertebrate Hbs range from single-chain globins found in bacteria, algae, protozoa, and plants to large, multisubunit, multidomain Hbs found in nematodes, molluscs a...

    journal_title:Physiological reviews

    pub_type: 杂志文章,评审

    doi:10.1152/physrev.2001.81.2.569

    authors: Weber RE,Vinogradov SN

    更新日期:2001-04-01 00:00:00

  • SIRT6, a Mammalian Deacylase with Multitasking Abilities.

    abstract::Mammalian sirtuins have emerged in recent years as critical modulators of multiple biological processes, regulating cellular metabolism, DNA repair, gene expression, and mitochondrial biology. As such, they evolved to play key roles in organismal homeostasis, and defects in these proteins have been linked to a plethor...

    journal_title:Physiological reviews

    pub_type: 杂志文章,评审

    doi:10.1152/physrev.00030.2018

    authors: Chang AR,Ferrer CM,Mostoslavsky R

    更新日期:2020-01-01 00:00:00

  • Glial calcium: homeostasis and signaling function.

    abstract::Glial cells respond to various electrical, mechanical, and chemical stimuli, including neurotransmitters, neuromodulators, and hormones, with an increase in intracellular Ca2+ concentration ([Ca2+]i). The increases exhibit a variety of temporal and spatial patterns. These [Ca2+]i responses result from the coordinated ...

    journal_title:Physiological reviews

    pub_type: 杂志文章,评审

    doi:10.1152/physrev.1998.78.1.99

    authors: Verkhratsky A,Orkand RK,Kettenmann H

    更新日期:1998-01-01 00:00:00

  • Astrocyte reactivity and reactive astrogliosis: costs and benefits.

    abstract::Astrocytes are the most abundant cells in the central nervous system (CNS) that provide nutrients, recycle neurotransmitters, as well as fulfill a wide range of other homeostasis maintaining functions. During the past two decades, astrocytes emerged also as increasingly important regulators of neuronal functions inclu...

    journal_title:Physiological reviews

    pub_type: 杂志文章,评审

    doi:10.1152/physrev.00041.2013

    authors: Pekny M,Pekna M

    更新日期:2014-10-01 00:00:00

  • Oxygen sensing and molecular adaptation to hypoxia.

    abstract::This review focuses on the molecular stratagems utilized by bacteria, yeast, and mammals in their adaptation to hypoxia. Among this broad range of organisms, changes in oxygen tension appear to be sensed by heme proteins, with subsequent transfer of electrons along a signal transduction pathway which may depend on rea...

    journal_title:Physiological reviews

    pub_type: 杂志文章,评审

    doi:10.1152/physrev.1996.76.3.839

    authors: Bunn HF,Poyton RO

    更新日期:1996-07-01 00:00:00

  • The Pancreatic β-Cell: A Bioenergetic Perspective.

    abstract::The pancreatic β-cell secretes insulin in response to elevated plasma glucose. This review applies an external bioenergetic critique to the central processes of glucose-stimulated insulin secretion, including glycolytic and mitochondrial metabolism, the cytosolic adenine nucleotide pool, and its interaction with plasm...

    journal_title:Physiological reviews

    pub_type: 杂志文章,评审

    doi:10.1152/physrev.00009.2016

    authors: Nicholls DG

    更新日期:2016-10-01 00:00:00

  • Vagal Afferent Innervation of the Airways in Health and Disease.

    abstract::Vagal sensory neurons constitute the major afferent supply to the airways and lungs. Subsets of afferents are defined by their embryological origin, molecular profile, neurochemistry, functionality, and anatomical organization, and collectively these nerves are essential for the regulation of respiratory physiology an...

    journal_title:Physiological reviews

    pub_type: 杂志文章,评审

    doi:10.1152/physrev.00039.2015

    authors: Mazzone SB,Undem BJ

    更新日期:2016-07-01 00:00:00

  • Properties of the glomerular barrier and mechanisms of proteinuria.

    abstract::This review focuses on the intricate properties of the glomerular barrier. Other reviews have focused on podocyte biology, mesangial cells, and the glomerular basement membrane (GBM). However, since all components of the glomerular membrane are important for its function, proteinuria will occur regardless of which lay...

    journal_title:Physiological reviews

    pub_type: 杂志文章,评审

    doi:10.1152/physrev.00055.2006

    authors: Haraldsson B,Nyström J,Deen WM

    更新日期:2008-04-01 00:00:00

  • Genetic and functional changes in mitochondria associated with aging.

    abstract::This review is devoted to the molecular genetics and bioenergetics of human mitochondria related to the mechanism of aging. Morphological and functional changes of mitochondria associated with age and age-related disease are overviewed with special reference to the changes in enzymes encoded by mitochondrial-inherent ...

    journal_title:Physiological reviews

    pub_type: 杂志文章,评审

    doi:10.1152/physrev.1997.77.2.425

    authors: Ozawa T

    更新日期:1997-04-01 00:00:00

  • Cardiac ionic currents and acute ischemia: from channels to arrhythmias.

    abstract::The aim of this review is to provide basic information on the electrophysiological changes during acute ischemia and reperfusion from the level of ion channels up to the level of multicellular preparations. After an introduction, section II provides a general description of the ion channels and electrogenic transporte...

    journal_title:Physiological reviews

    pub_type: 杂志文章,评审

    doi:10.1152/physrev.1999.79.3.917

    authors: Carmeliet E

    更新日期:1999-07-01 00:00:00