'Rejuvenating' neurons to protect against Parkinson's disease

Genetic variants predisposing to celiac disease, Regulating insensitivity to DNA damage, Getting specific with miRNA production, Following mitochondria in mouse neurons and Recombinant RNA

NATURE AND THE NATURE RESEARCH JOURNALS PRESS RELEASE

For papers that will be published online on 10 June 2007

This press release is copyrighted to the Nature journals mentioned below.

This press release contains:

· Summaries of newsworthy papers:

'Rejuvenating' neurons to protect against Parkinson's disease – Nature

Genetic variants predisposing to celiac disease – Nature Genetics

Regulating insensitivity to DNA damage – Nature Immunology

Getting specific with miRNA production – Nature Structural & Molecular Biology

Following mitochondria in mouse neurons – Nature Methods

Recombinant RNA – Nature Methods

· Mention of papers to be published at the same time with the same embargo

· Geographical listing of authors

PDFs of all the papers mentioned on this release can be found in the relevant journal’s section of http://press.nature.com. Press contacts for the Nature journals are listed at the end of this release.

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(http://www.nature.com/nature)

[1] Neurophysiology: 'Rejuvenating' neurons to protect against Parkinson's disease

DOI: 10.1038/nature05865

Encouraging neurons to revert to a more juvenile state might help slow or stop the progression of Parkinson's disease. Using mouse models of Parkinson’s disease, James Surmeier and colleagues report that blocking calcium channels with a commonly used drug 'rejuvenates' the dopamine-containing neurons that are typically affected by the disorder.

Parkinson's disease is a neurodegenerative disorder characterized by the death of dopamine-containing neurons in a region of the brain called the substantia nigra — but why these neurons are particularly vulnerable remains unclear. This research shows that these neurons rely on calcium channels to maintain their rhythmic activity. This reliance increases with age and leads to sustained elevations in cytosolic Ca2+, which could ultimately be detrimental to the cells. By blocking calcium channels in adult neurons — in both in vitro and in vivo mouse models — the authors were able to induce a more juvenile form of neural activity, forcing the neurons to use other ion channels and protecting them against disease progression.

The authors, whose findings are published online in Nature this week, speculate that these findings point to a potential therapeutic strategy that might protect against Parkinson's disease in humans, and possibly also broaden the therapeutic window for patients in the early stages of the disease.

Author contact:

James Surmeier (Northwestern University, Chicago, IL, USA)

Tel: +1 312 503 4904; E-mail: [email protected]

***********************************************NATURE GENETICS **************************************

(http://www.nature.com/naturegenetics)

[2] Genetic variants predisposing to coeliac disease

DOI: 10.1038/ng2058

A region containing four closely linked genes on chromosome 4 harbours variants that protect against the development of coeliac disease, according to a study to be published online this week in Nature Genetics. Coeliac disease is an autoimmune disorder of the small intestine that is caused by a reaction to a gluten protein found in wheat, rye and barley, requiring affected individuals to eat a gluten-free diet.

David van Heel and colleagues carried out a genome-wide association study for coeliac disease, initially looking at a group of affected and unaffected individuals in the UK. In addition to associations in the HLA region, which had been reported previously, they identified a protective variant in a region that contains the genes IL2, IL21, TENR, and a predicted gene of unknown function, KIAA1109. This association was replicated in populations from the Netherlands and from Ireland. The genes IL2 and IL21 are considered the two most promising genes to explain the association, as they encode interleukin-2 and interleukin-21, proteins known to be involved in other intestinal inflammatory diseases. Further mapping of this region will be required to pin down the mechanisms by which these variants protect against coeliac disease.

Author contact:

David van Heel (Queen Mary University of London, UK)

Tel: +44 207 882 2330; E-mail: [email protected]

Additional media contact:

Alex Fernandes (Queen Mary University of London, UK)
Tel: +44 207 882 7910; E-mail: [email protected]

Other papers from Nature Genetics to be published online at the same time and with the same embargo:

[3] Intra- and intercellular RNA interference in Arabidopsis thaliana requires components of the microRNA and heterochromatic silencing pathways

DOI: 10.1038/ng2081

[4] The ciliary gene RPGRIP1L is mutated in cerebello-oculo-renal syndrome (Joubert syndrome type B) and Meckel syndrome

DOI: 10.1038/ng2039

[5] Mutations in the gene encoding the basal body protein RPGRIP1L, a nephrocystin-4 interactor, cause Joubert syndrome

DOI: 10.1038/ng2069

*******************************************NATURE IMMUNOLOGY ************************************

(http://www.nature.com/natureimmunology)

[6] Regulating insensitivity to DNA damage

DOI: 10.1038/ni1478

A protein commonly associated with B cell lymphomas suppresses elimination of ‘useful’ B cells that otherwise harbor damaged DNA, suggests a report published online this week in Nature Immunology.

In most cells, DNA damage triggers ‘sensors’ to halt cellular activity until the DNA damage is repaired. Ari Melnick and colleagues find that the protein Bcl-6 prevents the production of the DNA damage sensor, called ATR, in a select group of B cells called germinal center (GC) cells, which produce antibodies. In this setting Bcl-6 is beneficial to B cells that encounter foreign antigen and then undergo highly focused DNA mutations in antibody-encoding genes, a process normally required to generate highly effective antibodies. However, such DNA mutations can also lead to GC B cell death, potentially reducing the production of useful antibodies.

Melnick’s group shows that Bcl-6 can suppress activity of the ATR gene, which effectively ‘turns off’ the DNA damage sensor machinery and leaves the mutated GC B cells less prone to DNA damage-induced death. More generally, many B cell lymphomas display deregulated Bcl-6 expression and tolerate excessive DNA mutations, including those generated by radiation treatments. The new work suggests that manipulating Bcl-6 in lymphoma cells might render them more sensitive to irradiation.

Author contact:

Ari Melnick (Albert Einstein College of Medicine, Bronx, NY, USA)

Tel: +1 718 430 4238; Email: [email protected]

Other papers from Nature Immunology to be published online at the same time and with the same embargo:

[7] IgEb immune complexes activate macrophages through FcgammaRIV binding

DOI:10.1038/ni1477

**********************NATURE STRUCTURAL AND MOLECULAR BIOLOGY************************

(http://www.nature.com/natstructmolbiol)

[8] Getting specific with miRNA production

DOI: 10.1038/nsmb1250

The upregulation of a specific microRNA (miRNA) implicated in cancer development by a general RNA processing factor is examined online this week in Nature Structural & Molecular Biology.

miRNAs are small RNAs involved in down-regulating gene expression and have been implicated in a number of biological processes. Multiple miRNAs are often produced as a single cluster, which is then cut up to generate individual precursor fragments.

Javier Cáceres and Sonia Guil examine production of a specific miRNA called miR-18a. miR-18a is processed out of a cluster of six miRNAs suggested to be involved in oncogenesis. They find that hnRNPA1, a factor that has been implicated in RNA processing, specifically binds to the cluster containing miR-18a, and promotes production of miR-18a above other members of the cluster. This suggests a role for general processing factors as auxiliary factors that facilitate production of specific microRNAs.

Author contact:

Javier Caceres (MRC Human Genetics Unit, Edinburgh, UK)

Tel: +44 131 467 8426; E-mail: [email protected]

Other papers from Nature Structural & Molecular Biology to be published online at the same time and with the same embargo:

[9] Structural basis for DNA helix separation by a superfamily 2 helicase

DOI: 10.1038/nsmb1246

********************************************NATURE METHODS******************************************

(http://www.nature.com/nmeth)

[10] Following mitochondria in mouse neurons

DOI: 10.1038/nmeth1055

A set of tools to study transport of mitochondria in neurons is presented in the July issue of Nature Methods.

The proper function and distribution of mitochondria, the much-described ‘powerhouses of the cell’, are important in neuronal physiology. Disruptions of these organelles are suspected to play a role in the pathology associated with neurodegenerative conditions like amyotrophic lateral sclerosis, as well as Parkinson’s and Alzheimer’s diseases. But studies on the neuronal transport of mammalian mitochondria have largely been done in the tissue culture dish.

Jeff Lichtman and colleagues now present mice in which the neuronal mitochondria as well as the neurons themselves have been labelled with genetically-encoded fluorescent proteins. In contrast to a previously published report of similar transgenic mice, here the authors demonstrate the utility of these models to study axonal transport in vivo. The movement of mitochondria can be imaged either in live mice or in acute nerve-muscle explants, which more closely resemble the in vivo setting than isolated neuronal cells. The researchers were also able to damage selected nerves in vivo and study changes in transport of the mitochondria through the nerves in the damaged region.

Author contact:

Jeff Lichtman (Harvard University, Cambridge, MA, USA)

Tel: +1 617 496 8943; E-mail: [email protected]

[11] Recombinant RNA

DOI: 10.1038/nmeth1058

A new technique to express large amounts of structured RNA in cells, allowing a thorough study of its function, is presented online this week on Nature Methods.

RNA is so much more than just the messenger between DNA and protein; RNA molecules also regulate transcription, have a role in controlling translation, and act as enzymes. But to investigate RNA’s structure and function in detail one needs large quantities of pure RNA species, which are difficult to obtain with current in vitro synthesis methods. Frédéric Dardel and colleagues have now devised a technique that facilitates the production of large amounts of correctly folded RNA inside a cell.

The key aspect of the method is the incorporation of the RNA of interest into the scaffold of a cell’s own highly structured RNA molecule – thereby tricking the cell into thinking the foreign RNA is part of its own RNA molecule and consequently protecting it from intracellular digestion. Once this recombinant RNA is generated one can easily purify it, and separate the foreign RNA from the scaffold for further analysis of its structure and function.

Author contact:

Frédéric Dardel (Université Paris Descartes, France)

Tel: +33 1 53 73 15 76; E-mail: [email protected]

Other papers from Nature Methods to be published online at the same time and with the same embargo:

[12] Determination of the sites of tyrosine O-sulfation in peptides and proteins

DOI: 10.1038/nmeth1056

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Items from other Nature journals to be published online at the same time and with the same embargo:

NATURE CHEMICAL BIOLOGY (http://www.nature.com/nchembio)

[13] Small-molecule pheromones that control dauer development in Caenorhabditis elegans

DOI: 10.1038/nchembio.2007.3

Nature PHYSICS (http://www.nature.com/naturephysics)

[14] Quantum interference of photon pairs from two remote trapped atomic ions

DOI:10.1038/nphys644

[15] Pinch points and Kasteleyn transitions in kagome ice

DOI: 10.1038/nphys632

NATURE MATERIALS (http://www.nature.com/naturematerials)

[16] Warping a single Mn acceptor wave function by straining the GaAs host

DOI: 10.1038/nmat1936

[17] Substrate-induced magnetic ordering and switching of iron porphyrin molecules

DOI: 10.1038/nmat1932

[18] Self-healing materials with microvascular networks

DOI: 10.1038/nmat1934

[19] Synthetic pores with reactive signal amplifiers as artificial tongues

DOI: 10.1038/nmat1933

NATURE NANOTECHNOLOGY (http://www.nature.com/nnano)

[20] Bacteria-mediated delivery of nanoparticles and cargo into cells (N&V)

DOI: 10.1038/nnano.2007.149

Nature MEDICINE (http://www.nature.com/naturemedicine)

[21] Multifunctional TH1 cells define a correlate of vaccine-mediated protection against Leishmania major

DOI: 10.1038/nm1592

Nature NEUROSCIENCE (http://www.nature.com/natureneuroscience)

[22] Cannabinoids mediate analgesia largely via peripheral type 1 cannabinoid receptors in nociceptors
DOI: 10.1038/nn1916

[23] UNC-46 is required for trafficking of the vesicular GABA transporter
DOI: 10.1038/nn1920

[24] Regulation of T-type calcium channels by Rho-associated kinase
DOI: 10.1038/nn1921

[25] RECK modulates Notch signaling during cortical neurogenesis by regulating ADAM10 activity
DOI: 10.1038/nn1922

NATURE CELL BIOLOGY (http://www.nature.com/naturecellbiology)

[26] The ubiquitin-specific protease USP28 is required for MYC stability

DOI: 10.1038/ncb1601

[27] Threonine phosphorylation post-translationally regulates protein secretion in Pseudomonas aeruginosa

DOI: 10.1038/ncb1605

[28] Maximal chromosome compaction occurs by axial shortening in anaphase and depends on Aurora kinase

DOI: 10.1038/ncb1606

[29] Dishevelled promotes axon differentiation by regulating atypical protein kinase C

DOI: 10.1038/ncb1603

[30] Wnt signalling regulates paxillin ubiquitination essential for mesodermal cell motility

DOI: 10.1038/ncb1607

[31] Wurst is essential for airway clearance and respiratory-tube size control

DOI: 10.1038/ncb1611

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GEOGRAPHICAL LISTING OF AUTHORS

The following list of places refers to the whereabouts of authors on the papers numbered in this release. The listing may be for an author's main affiliation, or for a place where they are working temporarily. Please see the PDF of the paper for full details.

AUSTRIA
Innsbruck: 22

BELGIUM
Leuven: 16

CANADA:

Calgary: 24

CHINA
Shanghai: 29

FRANCE

Angers: 4

Grenoble: 15

Paris: 4, 11

Roscoff: 4

Strasbourg: 3

Tours: 4

GERMANY

Aachen: 25

Berlin: 17

Bonn: 31

Diusberg: 17

Düsseldorf: 4

Erlangen: 22

Frankfurt: 22

Goettingen: 31

Heidelberg: 22, 28

Mainz: 5, 22

Marburg: 26

Munich: 9

Schwabenheim: 31

IRELAND
Dublin: 2

ITALY
Busto Arsizio: 22
Pavia: 19

JAPAN

Aichi: 30

Kyoto: 25

Nagoya: 7

Shiga: 19

Tokyo: 7, 19, 30

NETHERLANDS

Amsterdam: 2, 26

Eindhoven: 16

Groningen: 2

Leiden: 2

Nijmegen: 5

Utrecht: 2, 5

RUSSIA

St Petersburg: 16

SWEDEN

Uppsala: 17

SWITZERLAND

Geneva: 19

Zurich: 28

TURKEY

Kurupelit: 5

UNITED KINGDOM

Birmingham: 1, 4

Cambridge: 2

Derby: 2

Didcot: 15

Edinburgh: 8

Leeds: 2, 4

London: 2, 15

Oxford: 2

Penarth: 2

Sheffield: 2

UNITED STATES OF AMERICA

Alabama

Birmingham: 7

California

Berkeley: 6, 12

Davis: 12

Illinois

Chicago: 1

Urbana: 18

Indiana

West Lafayette: 20

Iowa

Iowa City: 16

Maine

Bar Harbor: 10

Maryland

Bethesda: 21, 22

Massachusetts

Boston: 13, 26, 27

Cambridge: 10

Michigan

Ann Arbor: 4, 14

New York

Bronx: 6

Oklahoma

Oklahoma City; 12

Utah

Salt Lake City: 23

Washington

Seattle: 5, 21, 22

Wisconsin

Madison: 6

PRESS CONTACTS…

For media inquiries relating to embargo policy for all the Nature Research Journals:

Katherine Anderson (Nature London)

Tel: +44 20 7843 4502; E-mail: [email protected]

Ruth Francis (Senior Press Officer, Nature, London)

Tel: +44 20 7843 4562; E-mail: [email protected]

For media inquiries relating to editorial content/policy for the Nature Research Journals, please contact the journals individually:

Nature Cell Biology (London)

Bernd Pulverer

Tel: +44 20 7843 4892; E-mail: [email protected]

Nature Chemical Biology (Boston)

Andrea Garvey

Tel: +1 617 475 9241, E-mail: [email protected]

Nature Genetics (New York)

Orli Bahcall

Tel: +1 212 726 9311; E-mail: [email protected]

Nature Immunology (New York)

Laurie Dempsey

Tel: +1 212 726 9372; E-mail: [email protected]

Nature Materials (London)

Maria Bellantone

Tel: +44 20 7843 4556; E-mail: [email protected]

Nature Medicine (New York)

Juan Carlos Lopez

Tel: +1 212 726 9325; E-mail: [email protected]

Nature Methods (New York)

Allison Doerr

Tel: +1 212 726 9393; E-mail: [email protected]

Nature Nanotechnology (London)

Peter Rodgers
Tel: +44 20 7014 4019; Email: [email protected]

Nature Neuroscience (New York)

Sandra Aamodt (based in California)

Tel: +1 530 795 3256; E-mail: [email protected]

Nature Physics (London)

Alison Wright

Tel: +44 20 7843 4555; E-mail: [email protected]

Nature Structural & Molecular Biology (New York)

Michelle Montoya

Tel: +1 212 726 9326; E-mail: [email protected]

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Published: 10 Jun 2007

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