Disruption of TRPM6/TRPM7 complex formation by a mutation in the TRPM6 gene causes hypomagnesemia with secondary hypocalcemia.

Abstract:

:Impaired magnesium reabsorption in patients with TRPM6 gene mutations stresses an important role of TRPM6 (melastatin-related TRP cation channel) in epithelial magnesium transport. While attempting to isolate full-length TRPM6, we found that the human TRPM6 gene encodes multiple mRNA isoforms. Full-length TRPM6 variants failed to form functional channel complexes because they were retained intracellularly on heterologous expression in HEK 293 cells and Xenopus oocytes. However, TRPM6 specifically interacted with its closest homolog, the Mg(2+)-permeable cation channel TRPM7, resulting in the assembly of functional TRPM6/TRPM7 complexes at the cell surface. The naturally occurring S141L TRPM6 missense mutation abrogated the oligomeric assembly of TRPM6, thus providing a cell biological explanation for the human disease. Together, our data suggest an important contribution of TRPM6/TRPM7 heterooligomerization for the biological role of TRPM6 in epithelial magnesium absorption.

authors

Chubanov V,Waldegger S,Mederos y Schnitzler M,Vitzthum H,Sassen MC,Seyberth HW,Konrad M,Gudermann T

doi

10.1073/pnas.0305252101

keywords:

subject

Has Abstract

pub_date

2004-03-02 00:00:00

pages

2894-9

issue

9

eissn

0027-8424

issn

1091-6490

pii

0305252101

journal_volume

101

pub_type

杂志文章
  • Grain-boundary topological phase transitions.

    abstract::The formation and migration of disconnections (line defects constrained to the grain boundary [GB] plane with both dislocation and step character) control many of the kinetic and dynamical properties of GBs and the polycrystalline materials of which they are central constituents. We demonstrate that GBs undergo a fini...

    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.2017390117

    authors: Chen K,Srolovitz DJ,Han J

    更新日期:2020-12-29 00:00:00

  • Inducible response required for repair of low-dose radiation damage in human fibroblasts.

    abstract::Ionizing radiation (IR) induces a variety of DNA lesions among which DNA double-strand breaks (DSBs) are the biologically most significant. It is currently unclear if DSB repair is equally efficient after low and high doses. Here, we use gamma-H2AX, phospho-ATM (pATM), and 53BP1 foci analysis to monitor DSB repair. We...

    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.1002213107

    authors: Grudzenski S,Raths A,Conrad S,Rübe CE,Löbrich M

    更新日期:2010-08-10 00:00:00

  • Channels formed by botulinum, tetanus, and diphtheria toxins in planar lipid bilayers: relevance to translocation of proteins across membranes.

    abstract::The heavy chains of both botulinum neurotoxin type B and tetanus toxin form channels in planar bilayer membranes. These channels have pH-dependent and voltage-dependent properties that are remarkably similar to those previously described for diphtheria toxin. Selectivity experiments with anions and cations show that 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.82.6.1692

    authors: Hoch DH,Romero-Mira M,Ehrlich BE,Finkelstein A,DasGupta BR,Simpson LL

    更新日期:1985-03-01 00:00:00

  • Origin and dynamics of admixture in Brazilians and its effect on the pattern of deleterious mutations.

    abstract::While South Americans are underrepresented in human genomic diversity studies, Brazil has been a classical model for population genetics studies on admixture. We present the results of the EPIGEN Brazil Initiative, the most comprehensive up-to-date genomic analysis of any Latin-American population. A population-based ...

    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.1504447112

    authors: Kehdy FS,Gouveia MH,Machado M,Magalhães WC,Horimoto AR,Horta BL,Moreira RG,Leal TP,Scliar MO,Soares-Souza GB,Rodrigues-Soares F,Araújo GS,Zamudio R,Sant Anna HP,Santos HC,Duarte NE,Fiaccone RL,Figueiredo CA,Silva TM,

    更新日期:2015-07-14 00:00:00

  • Impaired metabolic modulation of alpha-adrenergic vasoconstriction in dystrophin-deficient skeletal muscle.

    abstract::The neuronal isoform of nitric oxide synthase (nNOS) is highly expressed in mammalian skeletal muscle, but its functional role has not been defined. NO has been implicated in the local metabolic regulation of blood flow in contracting skeletal muscle in part by antagonizing sympathetic vasoconstriction. We therefore h...

    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.95.25.15090

    authors: Thomas GD,Sander M,Lau KS,Huang PL,Stull JT,Victor RG

    更新日期:1998-12-08 00:00:00

  • Structural insights into phosphoinositide 3-kinase activation by the influenza A virus NS1 protein.

    abstract::Seasonal epidemics and periodic worldwide pandemics caused by influenza A viruses are of continuous concern. The viral nonstructural (NS1) protein is a multifunctional virulence factor that antagonizes several host innate immune defenses during infection. NS1 also directly stimulates class IA phosphoinositide 3-kinase...

    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.0910715107

    authors: Hale BG,Kerry PS,Jackson D,Precious BL,Gray A,Killip MJ,Randall RE,Russell RJ

    更新日期:2010-02-02 00:00:00

  • Major diversification of voltage-gated K+ channels occurred in ancestral parahoxozoans.

    abstract::We examined the origins and functional evolution of the Shaker and KCNQ families of voltage-gated K(+) channels to better understand how neuronal excitability evolved. In bilaterians, the Shaker family consists of four functionally distinct gene families (Shaker, Shab, Shal, and Shaw) that share a subunit structure co...

    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.1422941112

    authors: Li X,Liu H,Chu Luo J,Rhodes SA,Trigg LM,van Rossum DB,Anishkin A,Diatta FH,Sassic JK,Simmons DK,Kamel B,Medina M,Martindale MQ,Jegla T

    更新日期:2015-03-03 00:00:00

  • Methylated DNA-binding domain 1 and methylpurine-DNA glycosylase link transcriptional repression and DNA repair in chromatin.

    abstract::The methyl-CpG dinucleotide containing a symmetrical 5-methylcytosine (mC) is involved in gene regulation and genome stability. We report here that methylation-mediated transcriptional repressor methylated DNA-binding domain 1 (MBD1) interacts with methylpurine-DNA glycosylase (MPG), which excises damaged bases from s...

    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.2131819100

    authors: Watanabe S,Ichimura T,Fujita N,Tsuruzoe S,Ohki I,Shirakawa M,Kawasuji M,Nakao M

    更新日期:2003-10-28 00:00:00

  • In vivo assembly of rhodopsin from expressed polypeptide fragments.

    abstract::Rhodopsin folding and assembly were investigated by expression of five bovine opsin gene fragments separated at points corresponding to proteolytic cleavage sites in the second or third cytoplasmic regions. The CH(1-146) and CH(147-348) gene fragments encode amino acids 1-146 and 147-348 of opsin, while the TH(1-240) ...

    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.92.8.3204

    authors: Ridge KD,Lee SS,Yao LL

    更新日期:1995-04-11 00:00:00

  • Cleavage of the membrane precursor for transforming growth factor alpha is a regulated process.

    abstract::Transforming growth factor alpha (TGF-alpha) is generated by cleavage of a membrane-anchored precursor protein, proTGF-alpha. ProTGF-alpha is cleaved at a slow rate and accumulates on the cell surface, thereby mediating cell-cell adhesion and mitogenic stimulation. We show here that cleavage of membrane proTGF-alpha b...

    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.88.5.1726

    authors: Pandiella A,Massagué J

    更新日期:1991-03-01 00:00:00

  • Construction and cloning of rat albumin structural gene sequences.

    abstract::A recombinant plasmid containing a DNA segment complementary to rat liver albumin mRNA has been constructed, cloned, and used to examine the organization of albumin gene. The 18S fraction of total liver poly(A)-containing RNA was copied into a double-stranded cDNA by avian myeloblastosis virus reverse transcriptase an...

    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.76.9.4370

    authors: Kioussis D,Hamilton R,Hanson RW,Tilghman SM,Taylor JM

    更新日期:1979-09-01 00:00:00

  • Heterotypic and homotypic associations between ezrin and moesin, two putative membrane-cytoskeletal linking proteins.

    abstract::Ezrin and moesin are components of actin-rich cell surface structures that are thought to function as membrane-cytoskeletal linking proteins. Here we show that a stable complex of ezrin and moesin can be isolated from cultured cells by immunoprecipitation with specific antibodies. The capacity of these two proteins to...

    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.90.22.10846

    authors: Gary R,Bretscher A

    更新日期:1993-11-15 00:00:00

  • Stat3 and Stat4: members of the family of signal transducers and activators of transcription.

    abstract::The deduced amino acid sequence of two members of the signal transducers and activators of transcription (STAT) family from the mouse are described. Comparison with the deduced protein sequence of the two previously described genes (Stat91 and Stat113), discovered because of their activation as transcription factors 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.91.11.4806

    authors: Zhong Z,Wen Z,Darnell JE Jr

    更新日期:1994-05-24 00:00:00

  • Enhanced chemistry-climate feedbacks in past greenhouse worlds.

    abstract::Trace greenhouse gases are a fundamentally important component of Earth's global climate system sensitive to global change. However, their concentration in the pre-Pleistocene atmosphere during past warm greenhouse climates is highly uncertain because we lack suitable geochemical or biological proxies. This long-stand...

    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.1102409108

    authors: Beerling DJ,Fox A,Stevenson DS,Valdes PJ

    更新日期:2011-06-14 00:00:00

  • Studies on the expression of the beta nerve growth factor (NGF) gene in the central nervous system: level and regional distribution of NGF mRNA suggest that NGF functions as a trophic factor for several distinct populations of neurons.

    abstract::Beta nerve growth factor (NGF), a target-derived protein necessary for survival and development of sympathetic and sensory neurons, can also affect subpopulations of neurons in the central nervous system (CNS). Using a blot hybridization assay capable of detecting 10 fg of mRNA, we measured the levels of NGF mRNA in 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.83.8.2714

    authors: Shelton DL,Reichardt LF

    更新日期:1986-04-01 00:00:00

  • Global trends in nature's contributions to people.

    abstract::Declining biodiversity and ecosystem functions put many of nature's contributions to people at risk. We review and synthesize the scientific literature to assess 50-y global trends across a broad range of nature's contributions. We distinguish among trends in potential and realized contributions of nature, as well as ...

    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.2010473117

    authors: Brauman KA,Garibaldi LA,Polasky S,Aumeeruddy-Thomas Y,Brancalion PHS,DeClerck F,Jacob U,Mastrangelo ME,Nkongolo NV,Palang H,Pérez-Méndez N,Shannon LJ,Shrestha UB,Strombom E,Verma M

    更新日期:2020-12-22 00:00:00

  • Lagging adaptation to warming climate in Arabidopsis thaliana.

    abstract::If climate change outpaces the rate of adaptive evolution within a site, populations previously well adapted to local conditions may decline or disappear, and banked seeds from those populations will be unsuitable for restoring them. However, if such adaptational lag has occurred, immigrants from historically warmer 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.1406314111

    authors: Wilczek AM,Cooper MD,Korves TM,Schmitt J

    更新日期:2014-06-03 00:00:00

  • Polytypism, polymorphism, and superconductivity in TaSe(2-x)Te(x).

    abstract::Polymorphism in materials often leads to significantly different physical properties--the rutile and anatase polymorphs of TiO2 are a prime example. Polytypism is a special type of polymorphism, occurring in layered materials when the geometry of a repeating structural layer is maintained but the layer-stacking sequen...

    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.1502460112

    authors: Luo H,Xie W,Tao J,Inoue H,Gyenis A,Krizan JW,Yazdani A,Zhu Y,Cava RJ

    更新日期:2015-03-17 00:00:00

  • Molecular basis for AUXIN RESPONSE FACTOR protein interaction and the control of auxin response repression.

    abstract::In plants, the AUXIN RESPONSE FACTOR (ARF) transcription factor family regulates gene expression in response to auxin. In the absence of auxin, ARF transcription factors are repressed by interaction with AUXIN/INDOLE 3-ACETIC ACID (Aux/IAA) proteins. Although the C termini of ARF and Aux/IAA proteins facilitate their ...

    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.1400074111

    authors: Korasick DA,Westfall CS,Lee SG,Nanao MH,Dumas R,Hagen G,Guilfoyle TJ,Jez JM,Strader LC

    更新日期:2014-04-08 00:00:00

  • Brain white matter structure and COMT gene are linked to second-language learning in adults.

    abstract::Adult human brains retain the capacity to undergo tissue reorganization during second-language learning. Brain-imaging studies show a relationship between neuroanatomical properties and learning for adults exposed to a second language. However, the role of genetic factors in this relationship has not been investigated...

    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.1606602113

    authors: Mamiya PC,Richards TL,Coe BP,Eichler EE,Kuhl PK

    更新日期:2016-06-28 00:00:00

  • The impact of Miocene atmospheric carbon dioxide fluctuations on climate and the evolution of terrestrial ecosystems.

    abstract::The Miocene is characterized by a series of key climatic events that led to the founding of the late Cenozoic icehouse mode and the dawn of modern biota. The processes that caused these developments, and particularly the role of atmospheric CO2 as a forcing factor, are poorly understood. Here we present a CO2 record b...

    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.0708588105

    authors: Kürschner WM,Kvacek Z,Dilcher DL

    更新日期:2008-01-15 00:00:00

  • Identification of plant compounds that disrupt the insect juvenile hormone receptor complex.

    abstract::Insects impact human health through vector-borne diseases and cause major economic losses by damaging crops and stored agricultural products. Insect-specific growth regulators represent attractive control agents because of their safety to the environment and humans. We identified plant compounds that serve as juvenile...

    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.1424386112

    authors: Lee SH,Oh HW,Fang Y,An SB,Park DS,Song HH,Oh SR,Kim SY,Kim S,Kim N,Raikhel AS,Je YH,Shin SW

    更新日期:2015-02-10 00:00:00

  • Phase coexistence and connectivity in the apical membrane of polarized epithelial cells.

    abstract::Although it is well described in model membranes, little is known about phase separation in biological membranes. Here, we provide evidence for a coexistence of at least two different lipid bilayer phases in the apical plasma membrane of epithelial cells. Phase connectivity was assessed by measuring long-range diffusi...

    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.0509885103

    authors: Meder D,Moreno MJ,Verkade P,Vaz WL,Simons K

    更新日期:2006-01-10 00:00:00

  • Synthesis and bioassay of improved mosquito repellents predicted from chemical structure.

    abstract::Mosquito repellency data on acylpiperidines derived from the U.S. Department of Agriculture archives were modeled by using molecular descriptors calculated by CODESSA PRO software. An artificial neural network model was developed for the correlation of these archival results and used to predict the repellent activity ...

    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.0800571105

    authors: Katritzky AR,Wang Z,Slavov S,Tsikolia M,Dobchev D,Akhmedov NG,Hall CD,Bernier UR,Clark GG,Linthicum KJ

    更新日期:2008-05-27 00:00:00

  • Fighting fruit flies: a model system for the study of aggression.

    abstract::Despite the importance of aggression in the behavioral repertoire of most animals, relatively little is known of its proximate causation and control. To take advantage of modern methods of genetic analysis for studying this complex behavior, we have developed a quantitative framework for studying aggression in common ...

    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.082102599

    authors: Chen S,Lee AY,Bowens NM,Huber R,Kravitz EA

    更新日期:2002-04-16 00:00:00

  • Stopping the circadian pacemaker with inhibitors of protein synthesis.

    abstract::The requirement for protein synthesis in the mechanism of a circadian pacemaker was investigated by using inhibitors of protein synthesis. Continuous treatment of the ocular circadian pacemaker of the mollusc Bulla gouldiana with anisomycin or cycloheximide substantially lengthened (up to 39 and 52 hr, respectively) 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.89.22.10862

    authors: Khalsa SB,Whitmore D,Block GD

    更新日期:1992-11-15 00:00:00

  • Composition and distribution of low density lipoprotein fractions in hyperapobetalipoproteinemia, normolipidemia, and familial hypercholesterolemia.

    abstract::Hyperapobetalipoproteinemia is defined as the combination of a normal low density lipoprotein (LDL) cholesterol in the face of an increased LDL apolipoprotein B (apoB) protein. To examine the physical basis for the apparent disproportion between LDL cholesterol and apoB characteristic of this syndrome, we used density...

    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.80.21.6662

    authors: Teng B,Thompson GR,Sniderman AD,Forte TM,Krauss RM,Kwiterovich PO Jr

    更新日期:1983-11-01 00:00:00

  • Increased cell proliferation and neurogenesis in the adult human Huntington's disease brain.

    abstract::Neurogenesis has recently been observed in the adult human brain, suggesting the possibility of endogenous neural repair. However, the augmentation of neurogenesis in the adult human brain in response to neuronal cell loss has not been demonstrated. This study was undertaken to investigate whether neurogenesis occurs ...

    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.1532244100

    authors: Curtis MA,Penney EB,Pearson AG,van Roon-Mom WM,Butterworth NJ,Dragunow M,Connor B,Faull RL

    更新日期:2003-07-22 00:00:00

  • Coexistence of phycoerythrin and a chlorophyll a/b antenna in a marine prokaryote.

    abstract::Prochlorococcus marinus CCMP 1375, a ubiquitous and ecologically important marine prochlorophyte, was bound to possess functional genes coding for the alpha and beta subunits of a phycobiliprotein. The latter is similar to phycoerythrins (PE) from marine Synechococcus cyanobacteria and bind a phycourobilin-like pigmen...

    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.93.20.11126

    authors: Hess WR,Partensky F,van der Staay GW,Garcia-Fernandez JM,Börner T,Vaulot D

    更新日期:1996-10-01 00:00:00

  • The N-terminal amino-acid sequence of bovine proparathyroid hormone.

    abstract::Proparathyroid hormone (calcemic fraction-A) is a biosynthetic precursor of parathyroid hormone in bovine glands. Limited amounts of the isolated prohormone have been obtained for the purpose of initial structural studies. The results of automated sequence analysis on two separate preparations indicate that the N-term...

    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.71.3.653

    authors: Hamilton JW,Niall HD,Jacobs JW,Keutmann HT,Potts JT Jr,Cohn DV

    更新日期:1974-03-01 00:00:00