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. Mutations in the cytoplasmic nucleotide binding domains, including the common allele DeltaF508, decrease the efficiency of CFTR folding, reduce the probability of its dissociation from molecular chaperones, and largely prevent its maturation through the secretory pathway to the plasma membrane. These mutant CFTR molecules are rapidly degraded by cytoplasmic proteasomes by a process that requires covalent modification by multiubiquitination. The effects of temperature and chemical chaperones on the intracellular processing of mutant CFTR molecules suggest that strategies aimed at increasing the folding yield of this protein in vivo may eventually lead to the development of novel therapies for cystic fibrosis.
journal_name
Physiol Revjournal_title
Physiological reviewsauthors
Kopito RRdoi
10.1152/physrev.1999.79.1.S167subject
Has Abstractpub_date
1999-01-01 00:00:00pages
S167-73issue
1 Suppleissn
0031-9333issn
1522-1210journal_volume
79pub_type
杂志文章,评审abstract::Animals synchronize to the environmental day-night cycle by means of an internal circadian clock in the brain. In mammals, this timekeeping mechanism is housed in the suprachiasmatic nucleus (SCN) of the hypothalamus and is entrained by light input from the retina. One output of the SCN is a neural code for circadian ...
journal_title:Physiological reviews
pub_type: 杂志文章,评审
doi:10.1152/physrev.00027.2019
更新日期:2020-10-01 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::Angiotensin (ANG) II is a powerful and phylogenetically widespread stimulus to thirst and sodium appetite. When it is injected directly into sensitive areas of the brain, it causes an immediate increase in water intake followed by a slower increase in NaCl intake. Drinking is vigorous, highly motivated, and rapidly co...
journal_title:Physiological reviews
pub_type: 杂志文章,评审
doi:10.1152/physrev.1998.78.3.583
更新日期:1998-07-01 00:00:00
abstract::Mitogen-activated protein kinases (MAPK) are serine-threonine protein kinases that are activated by diverse stimuli ranging from cytokines, growth factors, neurotransmitters, hormones, cellular stress, and cell adherence. Mitogen-activated protein kinases are expressed in all eukaryotic cells. The basic assembly of MA...
journal_title:Physiological reviews
pub_type: 杂志文章,评审
doi:10.1152/physrev.1999.79.1.143
更新日期:1999-01-01 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::Intrarenal autoregulatory mechanisms maintain renal blood flow (RBF) and glomerular filtration rate (GFR) independent of renal perfusion pressure (RPP) over a defined range (80-180 mmHg). Such autoregulation is mediated largely by the myogenic and the macula densa-tubuloglomerular feedback (MD-TGF) responses that regu...
journal_title:Physiological reviews
pub_type: 杂志文章,评审
doi:10.1152/physrev.00042.2012
更新日期:2015-04-01 00:00:00
abstract::There are two main classes of hormones in insects: 1) the true hormones produced by epithelial glands and belonging to the ecdysteroids or juvenile hormones and 2) the neuropeptide hormones produced by neurosecretory cells. Members of these classes regulate physiological, developmental, and behavioral events in insect...
journal_title:Physiological reviews
pub_type: 杂志文章,评审
doi:10.1152/physrev.1997.77.4.963
更新日期:1997-10-01 00:00:00
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
更新日期:1997-07-01 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::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
更新日期:2020-01-01 00:00:00
abstract::The function and survival of all organisms is dependent on the dynamic control of energy metabolism, when energy demand is matched to energy supply. The AMP-activated protein kinase (AMPK) alphabetagamma heterotrimer has emerged as an important integrator of signals that control energy balance through the regulation o...
journal_title:Physiological reviews
pub_type: 杂志文章,评审
doi:10.1152/physrev.00011.2008
更新日期:2009-07-01 00:00:00
abstract::Polymers of deoxyhemoglobin S deform sickle cell anemia red blood cells into sickle shapes, leading to the formation of dense, dehydrated red blood cells with a markedly shortened life-span. Nearly four decades of intense research in many laboratories has led to a mechanistic understanding of the complex events leadin...
journal_title:Physiological reviews
pub_type: 杂志文章,评审
doi:10.1152/physrev.00052.2003
更新日期:2005-01-01 00:00:00
abstract::Long-chain fatty acids and lipids serve a wide variety of functions in mammalian homeostasis, particularly in the formation and dynamic properties of biological membranes and as fuels for energy production in tissues such as heart and skeletal muscle. On the other hand, long-chain fatty acid metabolites may exert toxi...
journal_title:Physiological reviews
pub_type: 杂志文章,评审
doi:10.1152/physrev.00003.2009
更新日期:2010-01-01 00:00:00
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
更新日期:2001-04-01 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::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::Cardiac myocytes rapidly proliferate during fetal life but exit the cell cycle soon after birth in mammals. Although the extent to which adult cardiac myocytes are capable of cell cycle reentry is controversial and species-specific differences may exist, it appears that for the vast majority of adult cardiac myocytes ...
journal_title:Physiological reviews
pub_type: 杂志文章,评审
doi:10.1152/physrev.00032.2006
更新日期:2007-04-01 00:00:00
abstract::The key role of vitamin A in embryonal development is reviewed. Special emphasis is given to the physiological action of retinoids, as evident from the retinoid ligand knockout models. Retinoid metabolism in embryonic tissues and teratogenic consequences of retinoid administration at high doses are presented. Physiolo...
journal_title:Physiological reviews
pub_type: 杂志文章,评审
doi:10.1152/physrev.2000.80.3.1021
更新日期:2000-07-01 00:00:00
abstract::The iron hormone hepcidin and its receptor and cellular iron exporter ferroportin control the major fluxes of iron into blood plasma: intestinal iron absorption, the delivery of recycled iron from macrophages, and the release of stored iron from hepatocytes. Because iron losses are comparatively very small, iron absor...
journal_title:Physiological reviews
pub_type: 杂志文章,评审
doi:10.1152/physrev.00008.2013
更新日期:2013-10-01 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 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
更新日期:2016-10-01 00:00:00
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
更新日期:1997-04-01 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
abstract::This review focused on results obtained with methods that allow studies of ionic channels in situ, namely, patch clamping and current-noise analysis. We reported findings for ionic channels in apical and basolateral plasma membranes of various tight and leaky epithelia from a wide range of animal species and tissues. ...
journal_title:Physiological reviews
pub_type: 杂志文章,评审
doi:10.1152/physrev.1985.65.4.833
更新日期:1985-10-01 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::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::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::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::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
更新日期:1995-07-01 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