Highlights from Nature (10 July 2005) and August issue of Nature Research Journals

SARS receptor identified in vivo; Insights into the carbon trade; Nitric oxide targets cysteine; Understanding a side effect of TZDs; TACI is mutant in common variable immunodeficiency and IgA deficiency; Genetic influences on anxiety.

Insights into the carbon trade – Nature
Nitric oxide targets cysteine – Nature Chemical Biology
SARS receptor identified in vivo – Nature Medicine
Understanding a side effect of TZDs – Nature Medicine
TACI is mutant in common variable immunodeficiency and IgA deficiency – Nature Genetics
Genetic influences on anxiety – Nature Neuroscience


[1] Insights into the carbon trade

DOI: 10.1038/nature03835

In order to survive in dry conditions, plants must cautiously control the process of transpiration, by which they release water and can take up carbon at the same time. This trade-off was thought to be under genetic control, but pin-pointing the related DNA remained difficult. Now, a paper appearing online in Nature (10 July 2005) reports the finding of a gene called ERECTA that regulates transpiration efficiency. Josette Masle and her colleagues examined the carbon isotopic uptake of Arabidopsis plants to help them explain the variation in transpiration efficiency among these plants. As a result, researchers now know that the ERECTA gene can influence the coordination of transpiration and photosynthesis. The team goes one step further to show that ERECTA modifies this efficiency by changing how porous leaves are. They have also identified homologues of this gene in diverse species.

Author contact:
Josette Masle (The Australian National University, Canberra, Australia)
Tel: +61 2 6125 4410, E-mail: [email protected]

*************************************NATURE CHEMICAL BIOLOGY ***********************************

[3] Nitric oxide targets cysteine

DOI: 10.1038/nchembio720

Thioredoxin can catalyze the addition of nitric oxide to a unique active site cysteine in caspase-3, according to a paper in the August issue of Nature Chemical Biology. Protein S-nitrosation, the addition of nitric oxide (NO) to cysteines, is well established as an important signaling mechanism in vivo. However, unlike other post-translational modifications that are tightly regulated, the cellular mechanisms for catalyzing the precise addition and deletion of these NO groups had not been established.
S-nitrosation of the active site cysteine of caspase-3 in activates the enzyme and is known to be important in regulating apoptosis. Marletta and colleagues now show that thioredoxin can catalyze the transnitrosation—transfer of an NO group from a cysteine on one protein to that on another— of caspase-3. Unlike a solution reaction with NO, which results in the nitrosation of multiple cysteines in caspase-3, thioredoxin transfers the NO group exclusively to the active site cysteine.
This study opens the door to studying precise cellular pathways for protein S-nitrosation in vivo, and may reveal new opportunities small molecule modulation of signaling events like apoptosis.

Author contact:
Michael Marletta (University of California, Berkeley, CA, USA)
Tel: +1 510 643 9325, E-mail: [email protected]

************************************************NATURE MEDICINE***************************************

[4] SARS receptor identified in vivo

DOI: 10.1038/nm1267

A paper in the August issue of Nature Medicine reports that angiotensin-converting enzyme 2 (ACE2) is a crucial receptor of the severe acute respiratory syndrome (SARS) virus in vivo.
In 2003, a new pathogen—the SARS virus—spread rapidly through the world, causing severe pneumonia and lethal lung failure. In cell lines, ACE2, a protein well known for its role in regulating blood pressure, had been identified as a potential SARS receptor. Now, Josef Penninger and colleagues provide the first genetic proof that ACE2 is the SARS receptor in vivo.
They found that SARS infections and the Spike protein of the SARS virus reduce ACE2 expression, leading to leak from lung blood vessels and subsequent damage. Injection of the Spike protein into mice worsens acute lung failure in vivo, an effect that can be attenuated by blocking the renin-angiotensin pathway, through which ACE2 normally works.
The findings of Penninger and colleagues provide a molecular explanation for why SARS infections cause severe lung failure and suggest a rational therapy for SARS and possibly other respiratory disease viruses. In fact, a paper from the same group published in the 7 July issue of Nature (436. pp111-115) shows that ACE2 can also protect mice from severe acute lung failure induced by acute respiratory distress syndrome (ARDS).
A related News and Views article by John Nicholls and Malik Peiris, placing the findings in a broader context, will accompany this article.

Author contact:
Josef Penninger (Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Vienna, Austria)
Tel: + 43 1 797 30 454, E-mail: [email protected]

Additional contact for comment on paper:
John Nicholls (University of Hong Kong, China)
Tel: +852 2855 4875; E-mail: [email protected]

[5] Understanding a side effect of TZDs

DOI: 10.1038/nm1278

Thiazolidinediones (TZDs) are widely used to treat type-2 diabetes, but their use is complicated by systemic fluid retention. A paper in the August issue of Nature Medicine discloses the mechanism underlying this side effect.
In the kidney, the pharmacological target of TZDs, peroxisome proliferator-activated receptor-gamma (PPARg), is most abundant in the collecting duct of the nephron—the filtering unit of the kidney. Matthew Breyer and colleagues show that mice treated with TZDs retain water, an effect that was blocked by selective deletion of PPARg from the collecting duct. Deletion of PPARg decreased the transport of sodium through the sodium-selective channel Enac-g.
This study identifies Enac-g as a PPARg target in the collecting duct, suggesting that selective blockers of this channel might provide a specific therapy against fluid retention, an undesirable side effect of TZDs.

Author contact:
Matthew Breyer (Vanderbilt University, Nashville, TN, USA)
Tel: +1 615 343 3764, E-mail: [email protected]

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

[6] Intracellular protein therapy with SOCS3 inhibits inflammation and apoptosis
DOI: 10.1038/nm1269

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

[7] and [8] TACI is mutant in common variable immunodeficiency and IgA deficiency

[7] DOI: 10.1038/ng1601 &
[8] DOI: 10.1038/ng1600

In the August issue of Nature Genetics, two research studies present evidence for a new genetic factor underlying two human immunodeficiency syndromes. Common variable immunodeficiency (CVID), the most prevalent primary immunodeficiency, is characterized by various immune-system abnormalities and defective formation of all antibody types. A related syndrome, IgA deficiency (IgAD), is characterized by selective deficiency in IgA (immunoglobulin A) antibodies. IgA protects against infections of the mucous membranes lining the mouth, airways and digestive tract.
Bodo Grimbacher and colleagues report the identification of a gene defective in several families and unrelated individuals with CVID. In an accompanying study, Raif Geha and colleagues report defects in the same gene in individuals with either CVID or IgAD. The gene, encoding the protein TACI, is involved in switching between antibody types in antibody-producing white blood cells.
CVID and IgAD have common and diverse clinical presentations but are particularly characterized by increased risk of infection and autoimmune disorders. A mixture of genetic and environmental factors is thought to influence risk of developing these syndromes but the underlying genetic causes of CVID are largely unknown. CVID and IgAD are often found in the same families, and so a common genetic basis for these syndromes has long been suspected.

Author Contacts:
Bodo Grimbacher (University Hospital Freiburg, Germany)
Tel: +49 761 270 3696, E-mail: [email protected]

Raif S Geha (Children's Hospital, Boston, MA, USA)
Tel: +1 617 919 2482, E-mail: [email protected]

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

[9] Chromosome-wide and promoter-specific analyses identify sites of differential DNA methylation in normal and transformed human cells
DOI: 10.1038/ng1598

[10] Distinct epigenetic changes in the stromal cells of breast cancers
DOI: 10.1038/ng1596

*******************************************NATURE NEUROSCIENCE ***********************************

[11] Genetic influences on anxiety

DOI: 10.1038/nn1494

People with Williams syndrome, a genetic disorder that produces cognitive impairment and other symptoms, are extraordinarily sociable and outgoing, but also prone to excessive worrying. Brain areas involved in anxiety have abnormal activity in these individuals, according to a paper in the August issue of Nature Neuroscience. These findings may help pinpoint the neural circuits that are affected in this unusual genetic disorder.
Andreas Meyer-Lindenberg and colleagues imaged the brains of adults with Williams syndrome while they viewed images of emotional faces or scary scenes. The brain circuit that may be important for regulating emotional responses during threatening situations was less active for angry faces, but more for scary scenes. As Williams syndrome is transmitted genetically, the authors suggest that these results may shed light on how genes alter the function of brain mechanisms of social and emotional behavior.

Author contact:
Andreas Meyer-Lindenberg (Clinical Brain Disorders Branch, IRP, Bethesda, MD, USA)
Tel: +1 301 496 9672; E-mail: [email protected]

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

[12] Persistent hippocampal CA1 LTP in mice lacking the C-terminal PDZ ligand of GluR1
DOI: 10.1038/nn1432

[13] Mice lacking Dlx1 show subtype-specific loss of interneurons, reduced inhibition and epilepsy DOI: 10.1038/nn1499

[14] Stimulus context modulates competition in human extrastriate cortex
DOI: 10.1038/nn1501

[15] Cortical calcium waves in resting newborn mice
DOI: 10.1038/nn1502

[16] Probabilistic word pre-activation during language comprehension inferred from electrical brain activity
DOI: 10.1038/nn1504

Items from other Nature journals:

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

[17] Highly conductive nanolayers on strontium titanate produced by preferential ion-beam etching
DOI: 10.1038/nmat1402

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

[18] Structure and function of a potent agonist for the semi-invariant natural killer T cell receptor
DOI: 10.1038/ni1224

[19] The crystal structure of human CD1d with and without alpha-galactosylceramide
DOI: 10.1038/ni1225

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

[20] Protein kinase activity of phosphoinositide 3-kinase regulates beta-adrenergic receptor endocytosis
DOI: 10.1038/ncb1278

[21] Functional role of the AAA peroxins in dislocation of the cycling PTS1 receptor back to the cytosol
DOI: 10.1038/ncb1281

[22] Cdc2–cyclin E complexes regulate the G1/S phase transition
DOI: 10.1038/ncb1284

NATURE STRUCTURAL AND MOLECULAR BIOLOGY (http://www.nature.com/natstructmolbiol)

[23] Autoinhibition of X11/Mint scaffold proteins revealed by the closed conformation of the PDZ tandem
DOI: 10.1038/nsmb958

[24] The tumor suppressor p16INK4a prevents cell transformation through inhibition of c-Jun phosphorylation and AP-1 activity
DOI: 10.1038/nsmb960

[25] Diverse polyubiquitin interaction properties of ubiquitin-associated domains
DOI: 10.1038/nsmb962



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

Katharine Mansell (Nature London)
Tel: +44 20 7843 4658; E-mail: [email protected]

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

Nature Biotechnology (New York)
Kathy Aschheim
Tel: +1 212 726 9346; E-mail: [email protected]

Nature Cell Biology (London)
Bernd Pulverer
Tel: +44 20 7843 4892; E-mail: [email protected]

Nature Chemical Biology (Boston)
Beatrice Chrystall
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)
Ed Gerstner
Tel: +44 20 7843 4826; E-mail: [email protected]

Nature Medicine (New York)
Juan Carlos Lopez
Tel: +1 212 726 9325; E-mail: [email protected]

Nature Neuroscience (New York)
Sandra Aamodt (based in California)
Tel: +1 530 795 3256; E-mail: [email protected]

Nature Structural & Molecular Biology (New York)
Ed Feng
Tel: +1 212 726 9351; E-mail: [email protected]

Nature Publishing Group (NPG) is a division of Macmillan Publishers Ltd, dedicated to serving the academic and professional scientific community. NPG's flagship title, Nature, is the world's most highly-cited weekly multidisciplinary journal and was first published in 1869. Other publications include Nature research journals, Nature Reviews, Nature Clinical Practice, and a range of prestigious academic journals, including society-owned publications.

NPG is a global company, with headquarters in London and offices in New York, San Francisco, Washington DC, Boston, Tokyo, Paris, Munich and Basingstoke. For more information, please go to www.nature.com

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.

Warning: This document, and the Nature journal papers to which it refers, may contain information that is price sensitive (as legally defined, for example, in the UK Criminal Justice Act 1993 Part V) with respect to publicly quoted companies. Anyone dealing in securities using information contained in this document, or in advance copies of a Nature journal’s content, may be guilty of insider trading under the US Securities Exchange Act of 1934.

PICTURES: To obtain artwork from any of the journals, you must first obtain permission from the copyright holder (if named) or author of the research paper in question (if not).

NOTE: Once a paper is published, the digital object identifier (DOI) number can be used to retrieve the abstract and full text from the journal web site (abstracts are available to everyone, full text is available only to subscribers). To do this, add the DOI to the following URL: http://dx.doi.org/ (For example, http://dx.doi.org/10.1038/ng730). For more information about DOIs and Advance Online Publication, see http://www.nature.com/ng/aop/.

Published: 19 Jul 2005

Contact details:

The Macmillan Building, 4 Crinan Street
N1 9XW
United Kingdom

+44 20 7833 4000
News topics: 
Content type: 

Nature and Nature Research Journals