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1.
Tseng TT McMahon AM Johnson VT Mangubat EZ Zahm RJ Pacold ME Jakobsson E 《Journal of molecular microbiology and biotechnology》2007,12(3-4):249-262
Voltage-gated ion channels are well known for their functional roles in excitable tissues. Excitable tissues rely on voltage-gated ion channels and their auxiliary subunits to achieve concerted electrical activity in living cells. Auxiliary subunits are also known to provide functional diversity towards the transport and biogenesis properties of the principal subunits. Recent interests in pharmacological properties of these auxiliary subunits have prompted significant amounts of efforts in understanding their physiological roles. Some auxiliary subunits can potentially serve as drug targets for novel analgesics. Three families of sodium channel auxiliary subunits are described here: beta1 and beta3, beta2 and beta4, and temperature-induced paralytic E (TipE). While sodium channel beta-subunits are encoded in many animal genomes, TipE has only been found exclusively in insects. In this review, we present phylogenetic analyses, discuss potential evolutionary origins and functional data available for each of these subunits. For each family, we also correlate the functional specificity with the history of evolution for the individual auxiliary subunits. 相似文献
2.
Tseng TT McMahon AM Zahm RJ Pacold ME Jakobsson E 《Journal of molecular microbiology and biotechnology》2006,11(6):326-344
Many channels and carriers associate with auxiliary subunits which modify their activities and facilitate biogenesis. Advances in genome sequencing as well as biochemical, molecular genetic, and physiological experimentation have allowed for the discovery of many transport auxiliary subunits. Recent interests in the pharmacology of the calcium auxiliary subunits prompted a large amount of effort in deciphering their specific role in the conductance of calcium ions. In this review, we evaluate the functions of the 'extra' subunits of the voltage-gated calcium channels in animals as an example of auxiliary subunits of transporters in general. We discuss the functional data available for each of these subunits, present phylogenetic analyses, and discuss their potential evolutionary origins. Our analyses also reveal novel homologues of these subunits which might be of interest to the community. 相似文献
3.
Saier MH Eng BH Fard S Garg J Haggerty DA Hutchinson WJ Jack DL Lai EC Liu HJ Nusinew DP Omar AM Pao SS Paulsen IT Quan JA Sliwinski M Tseng TT Wachi S Young GB 《Biochimica et biophysica acta》1999,1422(1):1-56
As a result of recent genome sequencing projects as well as detailed biochemical, molecular genetic and physiological experimentation on representative transport proteins, we have come to realize that all organisms possess an extensive but limited array of transport protein types that allow the uptake of nutrients and excretion of toxic substances. These proteins fall into phylogenetic families that presumably reflect their evolutionary histories. Some of these families are restricted to a single phylogenetic group of organisms and may have arisen recently in evolutionary time while others are found ubiquitously and may be ancient. In this study we conduct systematic phylogenetic analyses of 26 families of transport systems that either had not been characterized previously or were in need of updating. Among the families analyzed are some that are bacterial-specific, others that are eukaryotic-specific, and others that are ubiquitous. They can function by either a channel-type or a carrier-type mechanism, and in the latter case, they are frequently energized by coupling solute transport to the flux of an ion down its electrochemical gradient. We tabulate the currently sequenced members of the 26 families analyzed, describe the properties of these families, and present partial multiple alignments, signature sequences and phylogenetic trees for them all. 相似文献
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With the astonishing rate that genomic and metagenomic sequence data sets are accumulating, there are many reasons to constrain the data analyses. One approach to such constrained analyses is to focus on select subsets of gene families that are particularly well suited for the tasks at hand. Such gene families have generally been referred to as “marker” genes. We are particularly interested in identifying and using such marker genes for phylogenetic and phylogeny-driven ecological studies of microbes and their communities (e.g., construction of species trees, phylogenetic based assignment of metagenomic sequence reads to taxonomic groups, phylogeny-based assessment of alpha- and beta-diversity of microbial communities from metagenomic data). We therefore refer to these as PhyEco (for phylogenetic and phylogenetic ecology) markers. The dual use of these PhyEco markers means that we needed to develop and apply a set of somewhat novel criteria for identification of the best candidates for such markers. The criteria we focused on included universality across the taxa of interest, ability to be used to produce robust phylogenetic trees that reflect as much as possible the evolution of the species from which the genes come, and low variation in copy number across taxa.We describe here an automated protocol for identifying potential PhyEco markers from a set of complete genome sequences. The protocol combines rapid searching, clustering and phylogenetic tree building algorithms to generate protein families that meet the criteria listed above. We report here the identification of PhyEco markers for different taxonomic levels including 40 for “all bacteria and archaea”, 114 for “all bacteria (greatly expanding on the ∼30 commonly used), and 100 s to 1000 s for some of the individual phyla of bacteria. This new list of PhyEco markers should allow much more detailed automated phylogenetic and phylogenetic ecology analyses of these groups than possible previously. 相似文献
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An important step to understanding ion channels is identifying the structural components that act as the gates to ion movement. Here we describe a new channel gating mechanism, produced by the beta3 auxiliary subunits of Ca2+-activated, large-conductance BK-type K+ channels when expressed with their pore-forming alpha subunits. BK beta subunits have a cysteine-rich extracellular segment connecting two transmembrane segments, with small cytosolic N and C termini. The extracellular segments of the beta3 subunits form gates to block ion permeation, providing a mechanism by which current can be rapidly diminished upon cellular repolarization. Furthermore, this gating mechanism is abolished by reduction of extracellular disulfide linkages, suggesting that endogenous mechanisms may regulate this gating behavior. The results indicate that auxiliary beta subunits of BK channels reside sufficiently close to the ion permeation pathway defined by the alpha subunits to influence or block access of small molecules to the permeation pathway. 相似文献
9.
Voltage-gated ion channels underlie electrical activity of neurons and are dynamically regulated by diverse cell signaling pathways that alter their phosphorylation state. Recent global mass spectrometric-based analyses of the mouse brain phosphoproteome have yielded a treasure trove of new data as to the extent and nature of phosphorylation of numerous ion channel principal or α subunits in mammalian brain. Here we compile and review data on 347 phosphorylation sites (261 unique) on 42 different voltage-gated ion channel α subunits that were identified in these recent studies. Researchers in the ion channel field can now begin to explore the role of these novel in vivo phosphorylation sites in the dynamic regulation of the localization, activity, and expression of brain ion channels through multisite phosphorylation of their principal subunits. 相似文献
10.
We define a novel superfamily of secondary carriers specific for cationic and anionic compounds, which we have termed the ion transporter (IT) superfamily. Twelve recognized and functionally defined families constitute this superfamily. We provide statistical sequence analyses demonstrating that these families were in fact derived from a common ancestor. Further, we characterize the 12 families in terms of (1) the known substrates transported, (2) the modes of transport and energy coupling mechanisms used, (3) the family sizes (in numbers of sequenced protein members in the current NCBI database), (4) the organismal distributions of the members of each family, (5) the size ranges of the constituent proteins, (6) the predicted topologies of these proteins, and (7) the occurrence of non-homologous auxiliary proteins that may either facilitate or be required for transport. No member of the superfamily is known to function in a capacity other than transport. Proteins in several of the constituent families are shown to have arisen by tandem intragenic duplication events, but topological variation has resulted from a variety of dissimilar genetic fusion, splicing and insertional events. The evolutionary relationships between the members of each family are defined, leading to predictions of functionally relevant orthologous relationships. Some but not all of the families include functionally dissimilar paralogues that arose by early extragenic duplication events. 相似文献
11.
Maue RA 《Journal of cellular physiology》2007,213(3):618-625
Epitope tags have been increasingly used to understand ion channel subunit assembly and interaction, trafficking, subcellular localization, and function in living cells. In particular, epitope tags have proven extremely useful for analyses of closely related, highly homologous channel subunits in endogenous cell contexts in vitro and in vivo, where multiple channel isoforms may be expressed. However, as the variety of epitope tags that have been used has expanded, and the use of tagged channel subunits has become increasingly sophisticated and widespread, there has also been an increase in the number of examples highlighting the potential problems associated with the use of epitope tags for ion channel studies. Described here are some of the epitope tags that have been used to study ion channel subunits, including the HA, FLAG, myc, His6, and green fluorescent protein (GFP) epitopes, as well as some of the applications and avenues of research in which they have proven advantageous. Potential pitfalls and caveats associated with the use of these epitope tags are also discussed, with an emphasis on the need to include careful characterization of epitope-tagged channel subunits as part of their construction. Finally, potential avenues for future investigation and the development of this approach are considered. 相似文献
12.
The mammalian CatSper ion channel family consists of four sperm-specific voltage-gated Ca2+ channels that are crucial for sperm hyperactivation and male fertility. All four CatSper subunits are believed to assemble into a heteromultimeric channel complex, together with an auxiliary subunit, CatSperbeta. Here, we report a comprehensive comparative genomics study and evolutionary analysis of CatSpers and CatSperbeta, with important correlation to physiological significance of molecular evolution of the CatSper channel complex. The development of the CatSper channel complex with four CatSpers and CatSperbeta originated as early as primitive metazoans such as the Cnidarian Nematostella vectensis. Comparative genomics revealed extensive lineage-specific gene loss of all four CatSpers and CatSperbeta through metazoan evolution, especially in vertebrates. The CatSper channel complex underwent rapid evolution and functional divergence, while distinct evolutionary constraints appear to have acted on different domains and specific sites of the four CatSper genes. These results reveal unique evolutionary characteristics of sperm-specific Ca2+ channels and their adaptation to sperm biology through metazoan evolution. 相似文献
13.
Evolutionary Relationship of the Ligand-Gated Ion Channels and the Avermectin-Sensitive,Glutamate-Gated Chloride Channels 总被引:4,自引:0,他引:4
Demetrios K. Vassilatis Keith O. Elliston Philip S. Paress Michel Hamelin Joseph P. Arena James M. Schaeffer Lex H.T. Van der Ploeg Doris F. Cully 《Journal of molecular evolution》1997,44(5):501-508
Two cDNAs, GluClα and GluClβ, encoding glutamate-gated chloride channel subunits that represent targets of the avermectin
class of antiparasitic compounds, have recently been cloned from Caenorhabditis elegans (Cully et al., Nature, 371, 707–711, 1994). Expression studies in Xenopus oocytes showed that GluClα and GluClβ have pharmacological profiles distinct from the glutamate-gated cation channels as
well as the γ-aminobutyric acid (GABA)- and glycine-gated chloride channels. Establishing the evolutionary relationship of
related proteins can clarify properties and lead to predictions about their structure and function. We have cloned and determined
the nucleotide sequence of the GluClα and GluClβ genes. In an attempt to understand the evolutionary relationship of these
channels with the members of the ligand-gated ion channel superfamily, we have performed gene structure comparisons and phylogenetic
analyses of their nucleotide and predicted amino acid sequences. Gene structure comparisons reveal the presence of several
intron positions that are not found in the ligand-gated ion channel superfamily, outlining their distinct evolutionary position.
Phylogenetic analyses indicate that GluClα and GluClβ form a monophyletic subbranch in the ligand-gated ion channel superfamily
and are related to vertebrate glycine channels/receptors. Glutamate-gated chloride channels, with electrophysiological properties
similar to GluClα and GluClβ, have been described in insects and crustaceans, suggesting that the glutamate-gated chloride
channel family may be conserved in other invertebrate species. The gene structure and phylogenetic analyses in combination
with the distinct pharmacological properties demonstrate that GluClα and GluClβ belong to a discrete ligand-gated ion channel
family that may represent genes orthologous to the vertebrate glycine channels.
Received: 30 September 1996 / Accepted: 15 November 1996 相似文献
14.
The voltage and time dependence of ion channels can be regulated, notably by phosphorylation, interaction with phospholipids,
and binding to auxiliary subunits. Many parameter variation studies have set conductance densities free while leaving kinetic
channel properties fixed as the experimental constraints on the latter are usually better than on the former. Because individual
cells can tightly regulate their ion channel properties, we suggest that kinetic parameters may be profitably set free during
model optimization in order to both improve matches to data and refine kinetic parameters. To this end, we analyzed the parameter
optimization of reduced models of three electrophysiologically characterized and morphologically reconstructed globus pallidus
neurons. We performed two automated searches with different types of free parameters. First, conductance density parameters
were set free. Even the best resulting models exhibited unavoidable problems which were due to limitations in our channel
kinetics. We next set channel kinetics free for the optimized density matches and obtained significantly improved model performance.
Some kinetic parameters consistently shifted to similar new values in multiple runs across three models, suggesting the possibility
for tailored improvements to channel models. These results suggest that optimized channel kinetics can improve model matches
to experimental voltage traces, particularly for channels characterized under different experimental conditions than recorded
data to be matched by a model. The resulting shifts in channel kinetics from the original template provide valuable guidance
for future experimental efforts to determine the detailed kinetics of channel isoforms and possible modulated states in particular
types of neurons. 相似文献
15.
Auxiliary Kvbeta subunits form complexes with Kv1 family voltage-gated K(+) channels by binding to a part of the N terminus of channel polypeptide. This association influences expression and gating of these channels. Here we show that Kv4.3 proteins are associated with Kvbeta2 subunits in the brain. Expression of Kvbeta1 or Kvbeta2 subunits does not affect Kv4.3 channel gating but increases current density and protein expression. The increase in Kv4.3 protein is larger at longer times after transfection, suggesting that Kvbeta-associated channel proteins are more stable than those without the auxiliary subunits. This association between Kv4.3 and Kvbeta subunits requires the C terminus but not the N terminus of the channel polypeptide. Thus, Kvbeta subunits utilize diverse molecular interactions to stimulate the expression of Kv channels from different families. 相似文献
16.
Nitrate transporters in plants: structure, function and regulation 总被引:43,自引:0,他引:43
Forde BG 《Biochimica et biophysica acta》2000,1465(1-2):219-235
Physiological studies have established that plants acquire their NO(-3) from the soil through the combined activities of a set of high- and low-affinity NO(-3) transport systems, with the influx of NO(-3) being driven by the H(+) gradient across the plasma membrane. Some of these NO(-3) transport systems are constitutively expressed, while others are NO(-3)-inducible and subject to negative feedback regulation by the products of NO(-3) assimilation. Here we review recent progress in the characterisation of the two families of NO(-3) transporters that have so far been identified in plants, their structure and their regulation, and consider the evidence for their roles in NO(-3) acquisition. We also discuss what is currently known about the genetic basis of NO(-3) induction and feedback repression of the NO(-3) transport and assimilatory pathway in higher plants. 相似文献
17.
The genetic and molecular basis of epilepsy 总被引:4,自引:0,他引:4
In the past decade, studies of large families in which epilepsy has been inherited in an autosomal dominant fashion have revealed several mutated genes, most of which encode ion channel subunits. Despite these exciting findings, only a few families with similar phenotypes have mutations in these known genes. More frustrating has been the genetic research into idiopathic epilepsies with complex inheritance. Although these forms are more common than those with Mendelian inheritance, their unknown mode of inheritance, phenotypic heterogeneity and the uncertainty of the genetic overlap among syndrome subtypes have hampered gene mapping. New techniques of molecular analysis could help the dissection of genes for epilepsies with complex inheritance. Hopefully, in the near future, successful genetic studies will make possible the discovery of new and more-targeted anti-epileptic drugs. 相似文献
18.
Wang Y Fu X Gaiser S Köttgen M Kramer-Zucker A Walz G Wegierski T 《The Journal of biological chemistry》2007,282(50):36561-36570
Transient receptor potential (TRP) proteins constitute a family of cation-permeable channels that are formed by homo- or heteromeric assembly of four subunits. Despite recent progress in the identification of protein domains required for the formation of tetramers, the mechanisms governing TRP channel assembly, and biogenesis in general, remain largely elusive. In particular, little is known about the involvement of regulatory proteins in these processes. Here we report that OS-9, a ubiquitously expressed endoplasmic reticulum (ER)-associated protein, interacts with the cytosolic N-terminal tail of TRPV4. Using a combination of co-expression and knockdown approaches we have found that OS-9 impedes the release of TRPV4 from the ER and reduces its amount at the plasma membrane. Consistent with these in vitro findings, OS-9 protected zebrafish embryos against the detrimental effects of TRPV4 expression in vivo. A detailed analysis of the underlying mechanisms revealed that OS-9 preferably binds TRPV4 monomers and other ER-localized, immature variants of TRPV4 and attenuates their polyubiquitination. Thus, OS-9 regulates the secretory transport of TRPV4 and appears to protect TRPV4 subunits from the precocious ubiquitination and ER-associated degradation. Our data suggest that OS-9 functions as an auxiliary protein for TRPV4 maturation. 相似文献
19.
The regulation of glutamate receptor trafficking and function by TARPs and other transmembrane auxiliary subunits 总被引:1,自引:0,他引:1
At excitatory synapses in the brain, glutamate released from nerve terminals binds to glutamate receptors to mediate signaling between neurons. Glutamate receptors expressed in heterologous cells show ion channel activity. Recently, native glutamate receptors were shown to contain auxiliary subunits that modulate the trafficking and/or channel properties. The AMPA receptor (AMPAR) can contain TARP and CNIHs as the auxiliary subunits, whereas kainate receptor (KAR) can contain the Neto auxiliary subunit. Each of these auxiliary subunits uniquely modulates the glutamate receptors, and determines properties of native glutamate receptors. A thorough elucidation of the properties of native glutamate receptor complexes is indispensable for the understanding of the molecular machinery that regulates glutamate receptors and excitatory synaptic transmission in the brain. 相似文献
20.
The Role of Auxiliary Subunits for the Functional Diversity of Voltage‐Gated Calcium Channels
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Voltage‐gated calcium channels (VGCCs) represent the sole mechanism to convert membrane depolarization into cellular functions like secretion, contraction, or gene regulation. VGCCs consist of a pore‐forming α1 subunit and several auxiliary channel subunits. These subunits come in multiple isoforms and splice‐variants giving rise to a stunning molecular diversity of possible subunit combinations. It is generally believed that specific auxiliary subunits differentially regulate the channels and thereby contribute to the great functional diversity of VGCCs. If auxiliary subunits can associate and dissociate from pre‐existing channel complexes, this would allow dynamic regulation of channel properties. However, most auxiliary subunits modulate current properties very similarly, and proof that any cellular calcium channel function is indeed modulated by the physiological exchange of auxiliary subunits is still lacking. In this review we summarize available information supporting a differential modulation of calcium channel functions by exchange of auxiliary subunits, as well as experimental evidence in support of alternative functions of the auxiliary subunits. At the heart of the discussion is the concept that, in their native environment, VGCCs function in the context of macromolecular signaling complexes and that the auxiliary subunits help to orchestrate the diverse protein–protein interactions found in these calcium channel signalosomes. Thus, in addition to a putative differential modulation of current properties, differential subcellular targeting properties and differential protein–protein interactions of the auxiliary subunits may explain the need for their vast molecular diversity. J. Cell. Physiol. 999: 00–00, 2015. © 2015 The Authors. Journal of Cellular Physiology Published by Wiley Periodicals, Inc. J. Cell. Physiol. 230: 2019–2031, 2015. © 2015 Wiley Periodicals, Inc. 相似文献