Evidence map›Paper›PMID 22328533›Full record

ArticleCirculation research2012

Actin cytoskeleton rest stops regulate anterograde traffic of connexin 43 vesicles to the plasma membrane.

James W Smyth, Jacob M Vogan, Pranali J Buch, Shan-Shan Zhang, Tina S Fong, Ting-Ting Hong, Robin M Shaw

Open access · bronzeAbstract read
In one paragraph

Article in Circulation research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 90 papers.

0numbers the graph read from it
0cells of the map it votes in
90citing papers in PubMed
6.7field-weighted citation impact, top 2% 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

90 citing papers in PubMed, 150 citations in OpenAlex.

  1. Article
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  7. Cx45 regulation by kinases and impact of expression in heart failure.Journal of molecular and cellular cardiology · 2025
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30 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 1 institution in 1 country.

James W SmythUniversity of California San Francisco, Cardiovascular Research Institute, 555 Mission Bay Boulevard South, San Francisco, CA 94158, USA.
Jacob M Vogan
Pranali J Buch
Shan-Shan Zhang
Tina S Fong
Ting-Ting Hong
Robin M Shaw
University of California, San Francisco · US

Funding

Novel Mechanisms of Cardiac Ion Channel RegulationR01HL094414 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI SHAW, ROBIN M · 2009 to 2018
$3.6M
BIN1 is a mediator and marker of cardiac reserve in heart failure.R00HL109075 · NHLBI · CEDARS-SINAI MEDICAL CENTER · PI HONG, TINGTING · 2013 to 2015
$730k
BIN1 is a mediator and marker of cardiac reserve in heart failure.K99HL109075 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI HONG, TINGTING · 2012 to 2013
$176k
NHLBI NIH HHS HL094414NHLBI NIH HHS K99 HL109075NHLBI NIH HHS R00 HL109075NHLBI NIH HHS R01 HL094414
6 · The paper itself

Abstract

rationaleThe intracellular trafficking of connexin 43 (Cx43) hemichannels presents opportunities to regulate cardiomyocyte gap junction coupling. Although it is known that Cx43 hemichannels are transported along microtubules to the plasma membrane, the role of actin in Cx43 forward trafficking is unknown.

objectiveWe explored whether the actin cytoskeleton is involved in Cx43 forward trafficking. METHODS AND

resultsHigh-resolution imaging reveals that Cx43 vesicles colocalize with nonsarcomeric actin in adult cardiomyocytes. Live-cell fluorescence imaging reveals Cx43 vesicles as stationary or traveling slowly (average speed 0.09 μm/s) when associated with actin. At any time, the majority (81.7%) of vesicles travel at subkinesin rates, suggesting that actin is important for Cx43 transport. Using Cx43 containing a hemagglutinin tag in the second extracellular loop, we developed an assay to detect transport of de novo Cx43 hemichannels to the plasma membrane after release from Brefeldin A-induced endoplasmic reticulum/Golgi vesicular transport block. Latrunculin A (for specific interference of actin) was used as an intervention after reinitiation of vesicular transport. Disruption of actin inhibits delivery of Cx43 to the cell surface. Moreover, using the assay in primary cardiomyocytes, actin inhibition causes an 82% decrease (P<0.01) in de novo endogenous Cx43 delivery to cell-cell borders. In Langendorff-perfused mouse heart preparations, Cx43/β-actin complexing is disrupted during acute ischemia, and inhibition of actin polymerization is sufficient to reduce levels of Cx43 gap junctions at intercalated discs.

conclusionsActin is a necessary component of the cytoskeleton-based forward trafficking apparatus for Cx43. In cardiomyocytes, Cx43 vesicles spend a majority of their time pausing at nonsarcomeric actin rest stops when not undergoing microtubule-based transport to the plasma membrane. Deleterious effects on this interaction between Cx43 and the actin cytoskeleton during acute ischemia contribute to losses in Cx43 localization at intercalated discs.

Indexed as

Actin CytoskeletonActinsAnimalsBiological TransportCell LineCell MembraneCells, CulturedConnexin 43Cytoplasmic VesiclesEndoplasmic ReticulumGap JunctionsGolgi ApparatusHumansKeratinocytesMiceMice, Inbred C57BLActinsConnexin 43

Identifiers

PMID22328533
PMCPMC3621031
OpenAlexW1978451664

What OpenQuestion holds

Textmetadata
LicenceTDM
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.