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1.
Hyperpolarization-activated and cyclic nucleotide-gated (HCN) channels belong to the superfamily of voltage-gated pore loop channels. HCN channels are unique among
vertebrate voltage-gated ion channels, in that they have a reverse voltage-dependence that leads to activation upon hyperpolarization.
In addition, voltage-dependent opening of these channels is directly regulated by the binding of cAMP. HCN channels are encoded
by four genes (HCN1–4) and are widely expressed throughout the heart and the central nervous system. The current flowing through
HCN channels, designated Ih or If, plays a key role in the control of cardiac and neuronal rhythmicity (“pacemaker current”). In addition, Ih contributes to several other neuronal processes, including determination of resting membrane potential, dendritic integration
and synaptic transmission. In this review we give an overview on structure, function and regulation of HCN channels. Particular
emphasis will be laid on the complex roles of these channels for neuronal function and cardiac rhythmicity.
Received 22 August 2008; received after revision 22 September 2008; accepted 24 September 2008 相似文献
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Correction to: The role of connexin proteins and their channels in radiation-induced atherosclerosis
Ramadan Raghda Baatout Sarah Aerts An Leybaert Luc 《Cellular and molecular life sciences : CMLS》2021,78(10):4847-4847
Cellular and Molecular Life Sciences - A correction to this paper has been published: https://doi.org/10.1007/s00018-021-03811-z 相似文献
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Huber O 《Cellular and molecular life sciences : CMLS》2003,60(9):1872-1890
Desmosomes represent major intercellular adhesive junctions at basolateral membranes of epithelial cells and in other tissues. They mediate direct cell-cell contacts and provide anchorage sites for intermediate filaments important for the maintenance of tissue architecture. There is increasing evidence now that desmosomes in addition to a simple structural function have new roles in tissue morphogenesis and differentiation. Transmembrane glycoproteins of the cadherin superfamily of Ca2+-dependent cell-cell adhesion molecules which mediate direct intercellular interactions in desmosomes appear to be of central importance in this respect. The complex network of proteins forming the desmosomal plaque associated with the cytoplasmic domain of the desmosomal cadherins, however, is also involved in junction assembly and regulation of adhesive strength. This re-view summarizes the structural features of these desmosomal proteins, their function during desmosome assembly and maintenance, and their role in development and disease.Received 5 February 2003; received after revision 14 March 2003; accepted 1 April 2003 相似文献
5.
A central dogma in biology is the conversion of genetic information into active proteins. The biosynthesis of proteins by
ribosomes and the subsequent folding of newly made proteins represent the last crucial steps in this process. To guarantee
the correct folding of newly made proteins, a complex chaperone network is required in all cells. In concert with ongoing
protein biosynthesis, ribosome-associated factors can interact directly with emerging nascent polypeptides to protect them
from degradation or aggregation, to promote folding into their native structure, or to otherwise contribute to their folding
program. Eukaryotic cells possess two major ribosome-associated systems, an Hsp70/Hsp40-based chaperone system and the functionally
enigmatic NAC complex, whereas prokaryotes employ the Trigger Factor chaperone. Recent structural insights into Trigger Factor
reveal an intricate cradle-like structure that, together with the exit site of the ribosome, forms a protected environment
for the folding of newly synthesized proteins.
Received 29 June 2005; received after revision 4 August 2005; accepted 18 August 2005 相似文献
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Martin Muik Rainer Schindl Marc Fahrner Christoph Romanin 《Cellular and molecular life sciences : CMLS》2012,69(24):4163-4176
Store-operated Ca2+ entry describes the phenomenon that connects a depletion of internal Ca2+ stores to an activation of plasma membrane-located Ca2+ selective ion channels. Tremendous progress towards the underlying molecular mechanism came with the discovery of the two respective limiting components, STIM and Orai. STIM1 represents the ER-located Ca2+ sensor and transmits the signal of store depletion to the plasma membrane. Here it couples to and activates Orai, the highly Ca2+-selective pore-forming subunit of Ca2+ release-activated Ca2+ channels. In this review, we focus on the molecular steps that these two proteins undergo from store-depletion to their coupling, the activation, and regulation of Ca2+ currents. 相似文献
8.
Esteva-Font C Ballarin J Fernández-Llama P 《Cellular and molecular life sciences : CMLS》2012,69(5):683-695
The kidney plays a central role in the regulation of the salt and water balance, which depends upon an array of solute and
water transporters in the renal tubules and upon vascular elements in the various regions of the kidney. Many recent studies
have improved our understanding of this process. In this review, we summarize the current data on the molecules involved in
sodium and water transport in the renal tubules, focusing in particular on aquaporins and renal sodium transporters and channels. 相似文献
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Dhar-Chowdhury P Malester B Rajacic P Coetzee WA 《Cellular and molecular life sciences : CMLS》2007,64(23):3069-3083
Glycolysis is an evolutionary conserved metabolic pathway that provides small amounts of energy in the form of ATP when compared
to other pathways such as oxidative phosphorylation or fatty acid oxidation. The ATP levels inside metabolically active cells
are not constant and the local ATP level will depend on the site of production as well as the respective rates of ATP production,
diffusion and consumption. Membrane ion transporters (pumps, exchangers and channels) are located at sites distal to the major
sources of ATP formation (the mitochondria). We review evidence that the glycolytic complex is associated with membranes;
both at the plasmalemma and with membranes of the endo/sarcoplasmic reticular network. We examine the evidence for the concept
that many of the ion transporters are regulated preferentially by the glycolytic process. These include the Na+/K+-ATPase, the H+-ATPase, various types of Ca2+-ATPases, the Na+/H+ exchanger, the ATP-sensitive K+ channel, cation channels, Na+ channels, Ca2+ channels and other channels involved in intracellular Ca2+ homeostasis. Regulation of these pumps, exchangers and ion channels by the glycolytic process has important consequences
in a variety of physiological and pathophysiological processes, and a better understanding of this mode of regulation may
have important consequences for developing future strategies in combating disease and developing novel therapeutic approaches.
Received 20 July 2007; received after revision 30 July 2007; accepted 17 August 2007 相似文献
12.
Molecular mechanisms of thrombin function 总被引:9,自引:0,他引:9
The discovery of thrombin as a Na+-dependent allosteric enzyme has revealed a novel strategy for regulating protease activity and specificity. The allosteric
nature of this enzyme influences all its physiologically important interactions and rationalizes a large body of structural
and functional information. For the first time, a coherent mechanistic framework is available for understanding how thrombin
interacts with fibrinogen, thrombomodulin and protein C, and how Na+ binding influences the specificity sites of the enzyme. This information can be used for engineering thrombin mutants with
selective specificity towards protein C and for the rational design of potent active site inhibitors. Thrombin also serves
as a paradigm for allosteric proteases. Elucidation of the molecular basis of the Na+-dependent allosteric regulation of catalytic activity, based on the residue present at position 225, provides unprecedented
insights into the function and evolution of serine proteases. This mechanism represents one of the simplest and most important
structure-function correlations ever reported for enzymes in general. All vitamin K-dependent proteases and some complement
factors are subject to the Na+-dependent regulation discovered for thrombin. Na+ is therefore a key factor in the activation of zymogens in the coagulation and complement systems. 相似文献
13.
Adducin: structure, function and regulation 总被引:7,自引:0,他引:7
Adducin is a ubiquitously expressed membrane-skeletal protein localized at spectrin-actin junctions that binds calmodulin and is an in vivo substrate for protein kinase C (PKC) and Rho-associated kinase. Adducin is a tetramer comprised of either alpha/beta or alpha/gamma heterodimers. Adducin subunits are related in sequence and all contain an N-terminal globular head domain, a neck domain and a C-terminal protease-sensitive tail domain. The tail domains of all adducin subunits end with a highly conserved 22-residue myristoylated alanine-rich C kinase substrate (MARCKS)-related domain that has homology to MARCKS protein. Adducin caps the fast-growing ends of actin filaments and also preferentially recruits spectrin to the ends of filaments. Both the neck and the MARCKS-related domains are required for these activities. The neck domain self-associates to form oligomers. The MARCKS-related domain binds calmodulin and contains the major phosphorylation site for PKC. Calmodulin, gelsolin and phosphorylation by the kinase inhibit in vitro activities of adducin involving actin and spectrin. Recent observations suggest a role for adducin in cell motility, and as a target for regulation by Rho-dependent and Ca2+-dependent pathways. Prominent physiological sites of regulation of adducin include dendritic spines of hippocampal neurons, platelets and growth cones of axons. 相似文献
14.
Novel regulation and function of Src tyrosine kinase 总被引:4,自引:0,他引:4
Src tyrosine kinase is a critical signal transducer that modulates a wide variety of cellular functions. Misregulation of
Src leads to cell transformation and cancer. Heterotrimeric guanine-nucleotide-binding proteins (G proteins) are another group
of signaling molecules that transduce signals from cell-surface receptors to generate physiological responses. Recently, it
was discovered that Gαs and Gαi could directly stimulate Src family tyrosine kinase activity. This novel regulation of Src
tyrosine kinase by G proteins provides insights into the adenylyl cyclase-independent signaling mechanisms involved in ligand-induced
receptor desensitization, internalization and other physiological processes.
Received 17 August 2001; received after revision 22 October 2001; accepted 24 October 2001 相似文献
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sHsps and their role in the chaperone network 总被引:17,自引:0,他引:17
Haslbeck M 《Cellular and molecular life sciences : CMLS》2002,59(10):1649-1657
Small Hsps (sHsps) encompass a widespread but diverse class of proteins. These low molecular mass proteins (15—42 kDa) form
dynamic oligomeric structures ranging from 9 to 50 subunits. sHsps display chaperone function in vitro, and in addition they
have been suggested to be involved in the inhibition of apoptosis, organisation of the cytoskeleton and establishing the refractive
properties of the eye lens in the case of α-crystallin. How these different functions can be explained by a common mechanism
is unclear at present. However, as most of the observed phenomena involve nonnative protein, the repeatedly reported chaperone
properties of sHsps seem to be of key importance for understanding their function. In contrast to other chaperone families,
sHsps bind several nonnative proteins per oligomeric complex, thus representing the most efficient chaperone family in terms
of the quantity of substrate binding. In some cases, the release of substrate proteins from the sHsp complex is achieved in
cooperation with Hsp70 in an ATP-dependent reaction, suggesting that the role of sHsps in the network of chaperones is to
create a reservoir of nonnative refoldable protein. 相似文献
17.
Interferon receptors and their role in interferon action 总被引:1,自引:0,他引:1
Interferon (IFN) proteins interact with cells through specific cell surface receptors, some of which have been purified and cloned. The alpha-IFNs and beta-IFN bind to a common receptor (type I), whereas gamma-IFN binds to a separate receptor (type II). Both types of high-affinity receptors have been demonstrated on a variety of receptors and the ways in which IFNs may affect cellular physiology and gene expression is discussed. 相似文献
18.
Dokland T 《Cellular and molecular life sciences : CMLS》1999,56(7-8):580-603
Scaffolding proteins are proteins that are required to catalyse, regulate or modulate some step in the assembly of a macromolecular complex. They associate specifically with the nascent protein complex during assembly, but are subsequently removed, and are absent from the mature structure. Scaffolding proteins have been described primarily from viral systems, in particular from the double-stranded DNA bacteriophages, but most likely play a more general role in macromolecular assembly, a fundamental process in all biological systems. Scaffolding proteins may act in a specific fashion, by actively encouraging the formation of correct protein-protein interactions, or more generally by nucleating and promoting assembly. They may also work to ensure the fidelity of the assembly process by preventing the formation of improper interactions, in many ways similar to the role of molecular chaperones in protein folding. In viruses, scaffolding proteins are found both in the form of internal cores and external bracing, and may form elaborate and complex structures. This review will focus on the viral scaffolding proteins, for which an increasing amount of structural and functional information has recently become available. 相似文献
19.
S. E. Grossberg J. L. Taylor V. M. Kushnaryov 《Cellular and molecular life sciences : CMLS》1989,45(6):508-513
Summary Interferon (IFN)_proteins interact with cells through specific cell surface receptors, some of which have been purified and cloned. The alpha-IFNs and beta-IFN bind to a common receptor (type I), whereas gamma-IFN binds to a separate receptor (type II). Both types of high-affinity receptors have been demonstrated on a variety of different kinds of cells but in relatively low numbers (102–104/cell). The relationship between IFN binding to receptors and the ways in which IFNs may affect cellular physiology and gene expression is discussed. 相似文献
20.
Chemokines are a vertebrate-specific group of small molecules that regulate cell migration and behaviour in diverse contexts.
So far, around 50 chemokines have been identified in humans, which bind to 18 different chemokine receptors. These are members
of the seven-transmembrane receptor family. Initially, chemokines were identified as modulators of the immune response. Subsequently,
they were also shown to regulate cell migration during embryonic development. Here, we discuss the influence of chemokines
and their receptors on angiogenesis, or the formation of new blood vessels. We highlight recent advances in our understanding
of how chemokine signalling might directly influence endothelial cell migration. We furthermore examine the contributions
of chemokine signalling in immune cells during this process. Finally, we explore possible implications for disease settings,
such as chronic inflammation and tumour progression. 相似文献