Alpha-actinin2 cytoskeletal protein is required for the functional membrane localization of a Ca2+-activated K+ channel (SK2 channel).

Abstract:

:The importance of proper ion channel trafficking is underpinned by a number of channel-linked genetic diseases whose defect is associated with failure to reach the cell surface. Conceptually, it is reasonable to suggest that the function of ion channels depends critically on the precise subcellular localization and the number of channel proteins on the cell surface membrane, which is determined jointly by the secretory and endocytic pathways. Yet the precise mechanisms of the entire ion channel trafficking pathway remain unknown. Here, we directly demonstrate that proper membrane localization of a small-conductance Ca(2+)-activated K(+) channel (SK2 or K(Ca)2.2) is dependent on its interacting protein, alpha-actinin2, a major F-actin crosslinking protein. SK2 channel localization on the cell-surface membrane is dynamically regulated, and one of the critical steps includes the process of cytoskeletal anchoring of SK2 channel by its interacting protein, alpha-actinin2, as well as endocytic recycling via early endosome back to the cell membrane. Consequently, alteration of these components of SK2 channel recycling results in profound changes in channel surface expression. The importance of our findings may transcend the area of K(+) channels, given that similar cytoskeletal interaction and anchoring may be critical for the membrane localization of other ion channels in neurons and other excitable cells.

authors

Lu L,Timofeyev V,Li N,Rafizadeh S,Singapuri A,Harris TR,Chiamvimonvat N

doi

10.1073/pnas.0908207106

subject

Has Abstract

pub_date

2009-10-27 00:00:00

pages

18402-7

issue

43

eissn

0027-8424

issn

1091-6490

pii

0908207106

journal_volume

106

pub_type

杂志文章
  • The Hawthorne effect and energy awareness.

    abstract::The feeling of being observed or merely participating in an experiment can affect individuals' behavior. Referred to as the Hawthorne effect, this inconsistently observed phenomenon can both provide insight into individuals' behavior and confound the interpretation of experimental manipulations. Here, we pursue both t...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1301687110

    authors: Schwartz D,Fischhoff B,Krishnamurti T,Sowell F

    更新日期:2013-09-17 00:00:00

  • Transdominant genetic analysis of a growth control pathway.

    abstract::Genetic selections that use proteinaceous transdominant inhibitors encoded by DNA libraries to cause mutant phenocopies may facilitate genetic analysis in traditionally nongenetic organisms. We performed a selection for random short peptides and larger protein fragments (collectively termed "perturbagens") that inhibi...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.95.13.7508

    authors: Caponigro G,Abedi MR,Hurlburt AP,Maxfield A,Judd W,Kamb A

    更新日期:1998-06-23 00:00:00

  • Phosphorylation/dephosphorylation of high-affinity IgE receptors: a mechanism for coupling/uncoupling a large signaling complex.

    abstract::Engagement of high-affinity IgE receptors leads to activation of tyrosine and serine/threonine kinases and the immediate phosphorylation of receptor beta (serine and tyrosine) and gamma (threonine and tyrosine) chains. Receptor disengagement leads to dephosphorylation of beta and gamma chains via the action of undefin...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.89.22.10733

    authors: Paolini R,Numerof R,Kinet JP

    更新日期:1992-11-15 00:00:00

  • Human--rat muscle somatic cell hybrids form myotubes and express human muscle gene products.

    abstract::Somatic cell hybrids have been prepared at high frequency between the rat muscle cell line L6 and human fetal muscle cells. The hybrid cells express several human gene products including an antigen, 12E7, controlled by the human X chromosome, Thy-1, and several human isoenzymes. In addition, one clone (37-11) expresse...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.78.8.5031

    authors: Quinn CA,Goodfellow PN,Povey S,Walsh FS

    更新日期:1981-08-01 00:00:00

  • Extreme rainfall activity in the Australian tropics reflects changes in the El Niño/Southern Oscillation over the last two millennia.

    abstract::Assessing temporal variability in extreme rainfall events before the historical era is complicated by the sparsity of long-term "direct" storm proxies. Here we present a 2,200-y-long, accurate, and precisely dated record of cave flooding events from the northwest Australian tropics that we interpret, based on an integ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1422270112

    authors: Denniston RF,Villarini G,Gonzales AN,Wyrwoll KH,Polyak VJ,Ummenhofer CC,Lachniet MS,Wanamaker AD Jr,Humphreys WF,Woods D,Cugley J

    更新日期:2015-04-14 00:00:00

  • Variable region genes for the immunoglobulin framework are assembled from small segments of DNA--a hypothesis.

    abstract::Sequences of each of the four framework segments FR1, FR2, FR3, and FR4 of the variable regions (V-regions) of light and heavy chains of immunoglobulins were grouped into sets with identical sequences. Sets contained from 1 to 18 members. When each V-region was traced from one FR to the next, it was seen that members ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.75.5.2429

    authors: Kabat EA,Wu TT,Bilofsky H

    更新日期:1978-05-01 00:00:00

  • Monoclonal antibodies reveal receptor specificity among G-protein-coupled receptor kinases.

    abstract::Guanine nucleotide-binding regulatory protein (G protein)-coupled receptor kinases (GRKs) constitute a family of serine/threonine kinases that play a major role in the agonist-induced phosphorylation and desensitization of G-protein-coupled receptors. Herein we describe the generation of monoclonal antibodies (mAbs) t...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.93.15.7649

    authors: Oppermann M,Diversé-Pierluissi M,Drazner MH,Dyer SL,Freedman NJ,Peppel KC,Lefkowitz RJ

    更新日期:1996-07-23 00:00:00

  • Energies and kinetics of radical pairs involving bacteriochlorophyll and bacteriopheophytin in bacterial reaction centers.

    abstract::Absorbance changes reflecting the formation of a transient radical-pair state, P(F), were measured in reaction centers from Rhodopseudomonas sphaeroides under conditions that blocked electron transfer to a later carrier (a quinone, Q). The temperature dependence of the absorbance changes suggests that P(F) is an equil...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.78.2.957

    authors: Shuvalov VA,Parson WW

    更新日期:1981-02-01 00:00:00

  • Extended survival of misfolded G85R SOD1-linked ALS mice by transgenic expression of chaperone Hsp110.

    abstract::Recent studies have indicated that mammalian cells contain a cytosolic protein disaggregation machinery comprised of Hsc70, DnaJ homologs, and Hsp110 proteins, the last of which acts to accelerate a rate-limiting step of nucleotide exchange of Hsc70. We tested the ability of transgenic overexpression of a Thy1 promote...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1604885113

    authors: Nagy M,Fenton WA,Li D,Furtak K,Horwich AL

    更新日期:2016-05-10 00:00:00

  • Tailor-made RNAi knockdown against triplet repeat disease-causing alleles.

    abstract::Nucleotide variations, including SNPs, in the coding regions of disease genes are important targets for RNAi treatment, which is a promising medical treatment for intractable diseases such as triplet repeat diseases. However, the identification of such nucleotide variations and the design of siRNAs conferring disease ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1012153107

    authors: Takahashi M,Watanabe S,Murata M,Furuya H,Kanazawa I,Wada K,Hohjoh H

    更新日期:2010-12-14 00:00:00

  • Myeloma proteins as tumor-specific transplantation antigens.

    abstract::BALB/c mice immunized with myeloma proteins 315 or 460 made antibodies to the individually specific ("idiotypic") determinants of these proteins and suppressed growth of the corresponding transplanted tumor cells (MOPC-315 or MOPC-460). Stable, variant MOPC-315 tumors that produce only the light chain of protein 315 g...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.69.6.1540

    authors: Lynch RG,Graff RJ,Sirisinha S,Simms ES,Eisen HN

    更新日期:1972-06-01 00:00:00

  • Structural insights into species-specific features of the ribosome from the pathogen Staphylococcus aureus.

    abstract::The emergence of bacterial multidrug resistance to antibiotics threatens to cause regression to the preantibiotic era. Here we present the crystal structure of the large ribosomal subunit from Staphylococcus aureus, a versatile Gram-positive aggressive pathogen, and its complexes with the known antibiotics linezolid a...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1517952112

    authors: Eyal Z,Matzov D,Krupkin M,Wekselman I,Paukner S,Zimmerman E,Rozenberg H,Bashan A,Yonath A

    更新日期:2015-10-27 00:00:00

  • Transcellular degradation of axonal mitochondria.

    abstract::It is generally accepted that healthy cells degrade their own mitochondria. Here, we report that retinal ganglion cell axons of WT mice shed mitochondria at the optic nerve head (ONH), and that these mitochondria are internalized and degraded by adjacent astrocytes. EM demonstrates that mitochondria are shed through f...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1404651111

    authors: Davis CH,Kim KY,Bushong EA,Mills EA,Boassa D,Shih T,Kinebuchi M,Phan S,Zhou Y,Bihlmeyer NA,Nguyen JV,Jin Y,Ellisman MH,Marsh-Armstrong N

    更新日期:2014-07-01 00:00:00

  • Design of yeast-secreted albumin derivatives for human therapy: biological and antiviral properties of a serum albumin-CD4 genetic conjugate.

    abstract::Due to its remarkably long half-life, together with its wide in vivo distribution and its lack of enzymatic or immunological functions, human serum albumin (HSA) represents an optimal carrier for therapeutic peptides/proteins aimed at interacting with cellular or molecular components of the vascular and interstitial c...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.89.5.1904

    authors: Yeh P,Landais D,Lemaître M,Maury I,Crenne JY,Becquart J,Murry-Brelier A,Boucher F,Montay G,Fleer R

    更新日期:1992-03-01 00:00:00

  • Mitochondrial DNA sequence evolution in the Arctoidea.

    abstract::Some taxa in the superfamily Arctoidea, such as the giant panda and the lesser panda, have presented puzzles to taxonomists. In the present study, approximately 397 bases of the cytochrome b gene, 364 bases of the 12S rRNA gene, and 74 bases of the tRNA(Thr) and tRNA(Pro) genes from the giant panda, lesser panda, kink...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.90.20.9557

    authors: Zhang YP,Ryder OA

    更新日期:1993-10-15 00:00:00

  • Human monoclonal antibodies produced by primary in vitro immunization of peripheral blood lymphocytes.

    abstract::A general procedure is described for the production of human monoclonal antibodies from peripheral blood lymphocytes immunized in vitro against T-cell-dependent antigens. These lymphocytes immunized in culture were used to produce human-human or human-mouse hybridomas secreting monoclonal antibodies specific for digox...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.85.11.3995

    authors: Borrebaeck CA,Danielsson L,Möller SA

    更新日期:1988-06-01 00:00:00

  • The remarkable influence of M2delta to thienyl pi conjugation in oligothiophenes incorporating MM quadruple bonds.

    abstract::Oligothiophenes incorporating MM quadruple bonds have been prepared from the reactions between Mo(2)(TiPB)(4) (TiPB = 2,4,6-triisopropyl benzoate) and 3',4'-dihexyl-2,2'-:5',2''-terthiophene-5,5''-dicarboxylic acid. The oligomers of empirical formula Mo(2)(TiPB)(2)(O(2)C(Th)-C(4)(n-hexyl)(2)S-(Th)CO(2)) are soluble in...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0807411105

    authors: Burdzinski GT,Chisholm MH,Chou PT,Chou YH,Feil F,Gallucci JC,Ghosh Y,Gustafson TL,Ho ML,Liu Y,Ramnauth R,Turro C

    更新日期:2008-10-07 00:00:00

  • Dynamic interplay between nitration and phosphorylation of tubulin cofactor B in the control of microtubule dynamics.

    abstract::Tubulin cofactor B (TCoB) plays an important role in microtubule dynamics by facilitating the dimerization of alpha- and beta-tubulin. Recent evidence suggests that p21-activated kinase 1 (Pak1), a major signaling nodule in eukaryotic cells, phosphorylates TCoB on Ser-65 and Ser-128 and plays an essential role in micr...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0705149104

    authors: Rayala SK,Martin E,Sharina IG,Molli PR,Wang X,Jacobson R,Murad F,Kumar R

    更新日期:2007-12-04 00:00:00

  • The genetic basis of a plant-insect coevolutionary key innovation.

    abstract::Ehrlich and Raven formally introduced the concept of stepwise coevolution using butterfly and angiosperm interactions in an attempt to account for the impressive biological diversity of these groups. However, many biologists currently envision butterflies evolving 50 to 30 million years (Myr) after the major angiosper...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0706229104

    authors: Wheat CW,Vogel H,Wittstock U,Braby MF,Underwood D,Mitchell-Olds T

    更新日期:2007-12-18 00:00:00

  • Structural and functional conservation of two human homologs of the yeast DNA repair gene RAD6.

    abstract::The RAD6 gene of Saccharomyces cerevisiae encodes a ubiquitin-conjugating enzyme (E2) that is required for DNA repair, damage-induced mutagenesis, and sporulation. We have cloned the two human RAD6 homologs, designated HHR6A and HHR6B. The two 152-amino acid human proteins share 95% sequence identity with each other a...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.88.20.8865

    authors: Koken MH,Reynolds P,Jaspers-Dekker I,Prakash L,Prakash S,Bootsma D,Hoeijmakers JH

    更新日期:1991-10-15 00:00:00

  • A peptide-based fluorescence resonance energy transfer assay for Bacillus anthracis lethal factor protease.

    abstract::A fluorescence resonance energy transfer assay has been developed for monitoring Bacillus anthracis lethal factor (LF) protease activity. A fluorogenic 16-mer peptide based on the known LF protease substrate MEK1 was synthesized and found to be cleaved by the enzyme at the anticipated site. Extension of this work to a...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.062171599

    authors: Cummings RT,Salowe SP,Cunningham BR,Wiltsie J,Park YW,Sonatore LM,Wisniewski D,Douglas CM,Hermes JD,Scolnick EM

    更新日期:2002-05-14 00:00:00

  • Functional interaction of erythropoietin and stem cell factor receptors is essential for erythroid colony formation.

    abstract::Production of mature erythrocytes requires multiple growth factors, but we do not know how their actions are coordinated. Here we show that erythroid progenitors from erythropoietin receptor (Epo-R)-/- fetal livers, infected in vitro with a retrovirus expressing the wild-type Epo-R, require addition of both Epo and st...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.94.5.1806

    authors: Wu H,Klingmüller U,Acurio A,Hsiao JG,Lodish HF

    更新日期:1997-03-04 00:00:00

  • Structural basis of nonnatural amino acid recognition by an engineered aminoacyl-tRNA synthetase for genetic code expansion.

    abstract::The genetic code in a eukaryotic system has been expanded by the engineering of Escherichia coli tyrosyl-tRNA synthetase (TyrRS) with the Y37V and Q195C mutations (37V195C), which specifically recognize 3-iodo-L-tyrosine rather than L-tyrosine. In the present study, we determined the 3-iodo-L-tyrosine- and L-tyrosine-...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0407039102

    authors: Kobayashi T,Sakamoto K,Takimura T,Sekine R,Kelly VP,Kamata K,Nishimura S,Yokoyama S

    更新日期:2005-02-01 00:00:00

  • Anatomy of funded research in science.

    abstract::Seeking research funding is an essential part of academic life. Funded projects are primarily collaborative in nature through internal and external partnerships, but what role does funding play in the formulation of these partnerships? Here, by examining over 43,000 scientific projects funded over the past three decad...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1513651112

    authors: Ma A,Mondragón RJ,Latora V

    更新日期:2015-12-01 00:00:00

  • The Order of the Antipode of Finite-dimensional Hopf Algebra.

    abstract::Examples of finite-dimensional Hopf algebras over a field, whose antipodes have arbitrary even orders >/=4 as mappings, are furnished. The dimension of the Hopf algebra is q(n+1), where the antipode has order 2q, q >/= 2, and n is an arbitrary positive integer. The algebras are not semisimple, and neither they nor the...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.68.11.2631

    authors: Taft EJ

    更新日期:1971-11-01 00:00:00

  • Inhibition and stimulation of the development of the bioluminescent system in Beneckea harveyi by cyclic GMP.

    abstract::The development of the luminescence system in Beneckea harveyi is controlled by cyclic nucleotides at the level of transcription. In the wild type, it is repressed by exogenously added guanosine 3':5'-cyclic monophosphate and this repression is overcome by the addition of adenosine 3':5'-cyclic monophosphate. These ob...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.73.12.4454

    authors: Ulitzur S,Yashphe J,Hastings JW

    更新日期:1976-12-01 00:00:00

  • Modulation of interleukin 2 receptor expression on normal human lymphocytes by thymic hormones.

    abstract::The expression of interleukin 2 receptors (IL-2R) is a critical step leading to normal lymphocyte proliferation. Since thymosin fraction 5 (TF5), a thymic hormone preparation, enhances lymphoproliferative responses of human cells, we examined the effects of TF5 on the expression of IL-2R on mitogen-stimulated human ly...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.83.16.6107

    authors: Sztein MB,Serrate SA,Goldstein AL

    更新日期:1986-08-01 00:00:00

  • Distinct geographic patterns of genetic diversity are maintained in wild barley (Hordeum vulgare ssp. spontaneum) despite migration.

    abstract::Mutations arise in a single individual and at a single point in time and space. The geographic distribution of mutations reflects both historical population size and frequency of migration. We employ coalescence-based methods to coestimate effective population size, frequency of migration, and level of recombination c...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1633708100

    authors: Morrell PL,Lundy KE,Clegg MT

    更新日期:2003-09-16 00:00:00

  • Natal dispersal driven by environmental conditions interacting across the annual cycle of a migratory songbird.

    abstract::Natal dispersal, the process through which immature individuals permanently depart their natal area in search of new sites, is integral to the ecology and evolution of animals. Insights about the underlying causes of natal dispersal arise mainly from research on species whose short dispersal distances or restricted di...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0710732105

    authors: Studds CE,Kyser TK,Marra PP

    更新日期:2008-02-26 00:00:00

  • Cre-mediated site-specific translocation between nonhomologous mouse chromosomes.

    abstract::Chromosome rearrangements, such as large deletions, inversions, or translocations, mediate migration of large DNA segments within or between chromosomes, which can have major effects on cellular genetic control. A method for chromosome manipulation would be very useful for studying the consequences of large-scale DNA ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.92.16.7376

    authors: Van Deursen J,Fornerod M,Van Rees B,Grosveld G

    更新日期:1995-08-01 00:00:00