Evidence map›Paper›PMID 22159083›Full record

ArticleAmerican journal of physiology. Cell physiology2012

Nongenomic STAT5-dependent effects on Golgi apparatus and endoplasmic reticulum structure and function.

Jason E Lee, Yang-Ming Yang, Feng-Xia Liang, Daniel J Gough, David E Levy, Pravin B Sehgal

Erratum issuedOpen access · greenAbstract read
In one paragraph

Article in American journal of physiology. Cell physiology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 38 papers.

0numbers the graph read from it
0cells of the map it votes in
38citing papers in PubMed
2.2field-weighted citation impact, top 13% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

38 citing papers in PubMed, 58 citations in OpenAlex.

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  15. Unlocking Golgi: Why Does Morphology Matter?Biochemistry. Biokhimiia · 2019
    Review
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4 · The record

Corrections and comments

  • Erratum issued
5 · Who and what money

Authors and funding

6 authors at 2 institutions in 1 country.

Jason E LeeDept. of Cell Biology & Anatomy, New York Medical College, Valhalla, NY 10595, USA.
Yang-Ming Yang
Feng-Xia Liang
Daniel J Gough
David E Levy
Pravin B Sehgal
New York Medical College · USNew York University · US

Funding

SIGNAL TRANSDUCTION PATHWAY IN IFN INDUCED TRANSCRIPTIONR01AI028900 · NIAID · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI LEVY, DAVID E · 1990 to 2010
$5.6M
Golgi Blockade in Pulmonary HypertensionR01HL087176 · NHLBI · NEW YORK MEDICAL COLLEGE · PI SEHGAL, PRAVIN B · 2008 to 2012
$2.0M
Second-hit and sexual dimorphism effects in PAHR03HL114609 · NHLBI · NEW YORK MEDICAL COLLEGE · PI SEHGAL, PRAVIN B · 2012 to 2013
$157k
Subcellular Mechanisms in Pathogenesis of Pulmonary Arterial HypertensionF31HL107013 · NHLBI · NEW YORK MEDICAL COLLEGE · PI LEE, JASON EDWARD · 2011 to 2012
$39k
NHLBI NIH HHS F31 HL107013NHLBI NIH HHS F31HL107013NHLBI NIH HHS R01 HL087176NHLBI NIH HHS R01HL087176NHLBI NIH HHS R03 HL114609NIAID NIH HHS R01AI28900
6 · The paper itself

Abstract

We report unexpected nongenomic functions of signal transducer and activator of transcription (STAT) 5 species in the cytoplasm aimed at preserving the structure and function of the Golgi apparatus and rough endoplasmic reticulum (ER) in vascular cells. Immunoimaging and green fluorescent protein-tagged-STAT5a protein localization studies showed the constitutive association of nonphosphorylated STAT5a, and to a lesser extent STAT5b, with the Golgi apparatus and of STAT5a with centrosomes in human pulmonary arterial endothelial and smooth muscle cells. Acute knockdown of STAT5a/b species using small interfering RNAs (siRNAs), including in the presence of an mRNA synthesis inhibitor (5,6-dichloro-1-β-d-ribofuranosylbenzimidazole), produced a dramatic phenotype within 1 day, consisting of dilatation and fragmentation of Golgi cisternae, a marked tubule-to-cyst change in the ER, increased accumulation of reticulon-4 (RTN4)/Nogo-B and atlastin-3 (ATL3) at cyst-zone boundaries, cystic separation of the outer and inner nuclear membranes, accompanied by scalloped/lunate distortion of the nucleus, with accumulation of RTN4 on convex sides of distorted nuclei. These cells showed inhibition of vesicular stomatitis virus G protein glycoprotein trafficking, mitochondrial fragmentation, and reduced mitochondrial function. STAT5a/b(-/-) mouse embryo fibroblasts also showed altered ER/Golgi dynamics. RTN4 knockdown using siRNA did not affect development of the cystic phenotype; ATL3 siRNA led to effacement of cyst-zone boundaries. In magnetic-bead cross-immunopanning assays, ATL3 bound both STAT5a and STAT5b. Remarkably, this novel cystic ER/lunate nucleus phenotype was characteristic of vascular cells in arterial lesions of idiopathic pulmonary hypertension, an unrelentingly fatal human disease. These data provide evidence of a STAT-family protein regulating the structure of a cytoplasmic organelle and implicate this mechanism in the pathogenesis of a human disease.

Indexed as

AnimalsCattleCell NucleusCells, CulturedCentrosomeCytoplasmDichlororibofuranosylbenzimidazoleEndoplasmic ReticulumEndothelial CellsFamilial Primary Pulmonary HypertensionGolgi ApparatusHumansHypertension, PulmonaryMembrane GlycoproteinsMiceMicroscopy, ElectronDichlororibofuranosylbenzimidazoleG protein, vesicular stomatitis virusMembrane GlycoproteinsMyelin ProteinsNogo ProteinsRNA, Small InterferingRTN4 protein, humanRtn4 protein, mouseSTAT5A protein, humanSTAT5B protein, humanSTAT5 Transcription FactorTumor Suppressor ProteinsViral Envelope Proteins

Identifiers

PMID22159083
PMCPMC3311300
OpenAlexW2078972545

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.