Abstract:
:Stress induced by accumulation of unfolded proteins at the endoplasmic reticulum (ER) is a classic feature of secretory cells and is observed in many tissues in human diseases including cancer, diabetes, obesity, and neurodegeneration. Cellular adaptation to ER stress is achieved by the activation of the unfolded protein response (UPR), an integrated signal transduction pathway that transmits information about the protein folding status at the ER to the nucleus and cytosol to restore ER homeostasis. Inositol-requiring transmembrane kinase/endonuclease-1 (IRE1α), the most conserved UPR stress sensor, functions as an endoribonuclease that processes the mRNA of the transcription factor X-box binding protein-1 (XBP1). IRE1α signaling is a highly regulated process, controlled by the formation of a dynamic scaffold onto which many regulatory components assemble, here referred to as the UPRosome. Here we provide an overview of the signaling and regulatory mechanisms underlying IRE1α function and discuss the emerging role of the UPR in adaptation to protein folding stress in specialized secretory cells and in pathological conditions associated with alterations in ER homeostasis.
journal_name
Physiol Revjournal_title
Physiological reviewsauthors
Hetz C,Martinon F,Rodriguez D,Glimcher LHdoi
10.1152/physrev.00001.2011subject
Has Abstractpub_date
2011-10-01 00:00:00pages
1219-43issue
4eissn
0031-9333issn
1522-1210pii
91/4/1219journal_volume
91pub_type
杂志文章,评审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
更新日期:2014-10-01 00:00:00
abstract::Propagation of excitation in the heart involves action potential (AP) generation by cardiac cells and its propagation in the multicellular tissue. AP conduction is the outcome of complex interactions between cellular electrical activity, electrical cell-to-cell communication, and the cardiac tissue structure. As shown...
journal_title:Physiological reviews
pub_type: 杂志文章,评审
doi:10.1152/physrev.00025.2003
更新日期:2004-04-01 00:00:00
abstract::For many decades, the inability of lesioned central neurons to regrow was accepted almost as a "law of nature", and on the clinical level, spinal cord and brain lesions were seen as being irreversible. Today we are starting to understand the mechanisms of neuronal regeneration in the central nervous system and its pre...
journal_title:Physiological reviews
pub_type: 杂志文章,评审
doi:10.1152/physrev.1996.76.2.319
更新日期:1996-04-01 00:00:00
abstract::Zinc is involved in a variety of biological processes, as a structural, catalytic, and intracellular and intercellular signaling component. Thus zinc homeostasis is tightly controlled at the whole body, tissue, cellular, and subcellular levels by a number of proteins, with zinc transporters being particularly importan...
journal_title:Physiological reviews
pub_type: 杂志文章,评审
doi:10.1152/physrev.00035.2014
更新日期:2015-07-01 00:00:00
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
更新日期:2016-07-01 00:00:00
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
更新日期:1998-10-01 00:00:00
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
更新日期:2018-01-01 00:00:00
abstract::While transport processes for amino acids and glucose have long been known to be expressed in the luminal and abluminal membranes of the endothelium comprising the blood-brain and blood-retinal barriers, it is only within the last decades that endothelial and smooth muscle cells derived from peripheral vascular beds h...
journal_title:Physiological reviews
pub_type: 杂志文章,评审
doi:10.1152/physrev.00022.2002
更新日期:2003-01-01 00:00:00
abstract::NHE3 is the brush-border (BB) Na(+)/H(+) exchanger of small intestine, colon, and renal proximal tubule which is involved in large amounts of neutral Na(+) absorption. NHE3 is a highly regulated transporter, being both stimulated and inhibited by signaling that mimics the postprandial state. It also undergoes downregu...
journal_title:Physiological reviews
pub_type: 杂志文章,评审
doi:10.1152/physrev.00030.2006
更新日期:2007-07-01 00:00:00
abstract::Biosynthesis and Degradation of CFTR. Physiol. Rev. 79, Suppl.: S167-S173, 1999. - Many of the mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene that cause cystic fibrosis interfere with the folding and biosynthetic processing of nascent CFTR molecules in the endoplasmic reticulum. Mutat...
journal_title:Physiological reviews
pub_type: 杂志文章,评审
doi:10.1152/physrev.1999.79.1.S167
更新日期:1999-01-01 00:00:00
abstract::The past two decades have witnessed an explosive growth of knowledge regarding postischemic myocardial dysfunction or myocardial "stunning." The purpose of this review is to summarize current information regarding the pathophysiology and pathogenesis of this phenomenon. Myocardial stunning should not be regarded as a ...
journal_title:Physiological reviews
pub_type: 杂志文章,评审
doi:10.1152/physrev.1999.79.2.609
更新日期:1999-04-01 00:00:00
abstract::Traditionally the auditory system was considered a hard-wired sensory system; this view has been challenged in recent years in light of the plasticity of other sensory systems, particularly the visual and somatosensory systems. Practical experience in clinical audiology together with the use of prosthetic devices, suc...
journal_title:Physiological reviews
pub_type: 杂志文章,评审
doi:10.1152/physrev.00002.2002
更新日期:2002-07-01 00:00:00
abstract::The vertebrate control of locomotion involves all levels of the nervous system from cortex to the spinal cord. Here, we aim to cover all main aspects of this complex behavior, from the operation of the microcircuits in the spinal cord to the systems and behavioral levels and extend from mammalian locomotion to the bas...
journal_title:Physiological reviews
pub_type: 杂志文章,评审
doi:10.1152/physrev.00015.2019
更新日期:2020-01-01 00:00:00
abstract::Intercellular calcium (Ca(2+)) waves (ICWs) represent the propagation of increases in intracellular Ca(2+) through a syncytium of cells and appear to be a fundamental mechanism for coordinating multicellular responses. ICWs occur in a wide diversity of cells and have been extensively studied in vitro. More recent stud...
journal_title:Physiological reviews
pub_type: 杂志文章,评审
doi:10.1152/physrev.00029.2011
更新日期:2012-07-01 00:00:00
abstract::Cutaneous melanin pigment plays a critical role in camouflage, mimicry, social communication, and protection against harmful effects of solar radiation. Melanogenesis is under complex regulatory control by multiple agents interacting via pathways activated by receptor-dependent and -independent mechanisms, in hormonal...
journal_title:Physiological reviews
pub_type: 杂志文章,评审
doi:10.1152/physrev.00044.2003
更新日期:2004-10-01 00:00:00
abstract::The life history of fibroblast and fibroblast-like cells includes an initial stage of outgrowth and establishment in culture; a period of vigorous proliferation which has a variable length, depending on the tissue of origin, age of the donor, etc.; a period of declining proliferative vigor which includes substantial c...
journal_title:Physiological reviews
pub_type: 杂志文章,评审
doi:10.1152/physrev.1993.73.3.617
更新日期:1993-07-01 00:00:00
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 R...
journal_title:Physiological reviews
pub_type: 杂志文章,评审
doi:10.1152/physrev.00003.2012
更新日期:2013-01-01 00:00:00
abstract::It has been suggested that highly social mammals, such as naked mole rats and humans, are long-lived due to neoteny (the prolongation of youth). In both species, aging cannot operate as a mechanism facilitating natural selection because the pressure of this selection is strongly reduced due to 1) a specific social str...
journal_title:Physiological reviews
pub_type: 杂志文章,评审
doi:10.1152/physrev.00040.2015
更新日期:2017-04-01 00:00:00
abstract::Molecular research on ion channels has demonstrated that many of these integral membrane proteins associate with partner proteins, often versatile in their function, or even assemble into stable macromolecular complexes that ensure specificity and proper rate of the channel-mediated signal transduction. Calcium-activa...
journal_title:Physiological reviews
pub_type: 杂志文章,评审
doi:10.1152/physrev.00049.2009
更新日期:2010-10-01 00:00:00
abstract::Impairments of vision and hearing are highly prevalent conditions limiting the quality of life and presenting a major socioeconomic burden. For a long time, retinal and cochlear disorders have remained intractable for causal therapies, with sensory rehabilitation limited to glasses, hearing aids, and electrical cochle...
journal_title:Physiological reviews
pub_type: 杂志文章,评审
doi:10.1152/physrev.00035.2019
更新日期:2020-10-01 00:00:00
abstract::Large-conductance Ca2+- and voltage-activated K+ (BK) channels play many physiological roles ranging from the maintenance of smooth muscle tone to hearing and neurosecretion. BK channels are tetramers in which the pore-forming α subunit is coded by a single gene (Slowpoke, KCNMA1). In this review, we first highlight t...
journal_title:Physiological reviews
pub_type: 杂志文章,评审
doi:10.1152/physrev.00001.2016
更新日期:2017-01-01 00:00:00
abstract::Reactive oxygen species (ROS) are generated as by-products of normal cellular metabolic activities. Superoxide dismutase, glutathione peroxidase, and catalase are the enzymes involved in protecting cells from the damaging effects of ROS. ROS are produced in response to ultraviolet radiation, cigarette smoking, alcohol...
journal_title:Physiological reviews
pub_type: 杂志文章,评审
doi:10.1152/physrev.00040.2012
更新日期:2014-04-01 00:00:00
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
更新日期:2002-10-01 00:00:00
abstract::The major areas of normal coronary physiological research since Berne's 1964 review have been the measurement of ventricular transmural blood flow distribution with microspheres, the adenosine hypothesis of local metabolic control of coronary blood flow, and the autonomic control of coronary blood flow. There is an im...
journal_title:Physiological reviews
pub_type: 杂志文章,评审
doi:10.1152/physrev.1983.63.1.1
更新日期:1983-01-01 00:00:00
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
更新日期:1999-07-01 00:00:00
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
更新日期:2008-04-01 00:00:00
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
更新日期:2018-01-01 00:00:00
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
更新日期:1996-10-01 00:00:00
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
更新日期:2005-07-01 00:00:00
abstract::A careful review of several different organs shows that with the information available today the beginnings of the microlymphatics in the tissue consist of endothelialized tubes only. Lymphatic smooth muscle within the collecting lymphatics appears further downstream, in some organs only outside the parenchyma. This p...
journal_title:Physiological reviews
pub_type: 杂志文章,评审
doi:10.1152/physrev.1990.70.4.987
更新日期:1990-10-01 00:00:00