Evidence map›Paper›PMID 28923791›Full record

ArticleCirculation research2017

GJA1-20k Arranges Actin to Guide Cx43 Delivery to Cardiac Intercalated Discs.

Wassim A Basheer, Shaohua Xiao, Irina Epifantseva, Ying Fu, Andre G Kleber, TingTing Hong, Robin M Shaw

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Circulation research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
73citing papers in PubMed, 1 pooled it
4.9field-weighted citation impact, top 4% 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

73 citing papers in PubMed, 1 synthesis or guideline pooled it, 98 citations in OpenAlex.

  1. Pooled it
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  10. Deceiving the gatekeepers: virus modulation of gap junctions.Microbiology and molecular biology reviews : MMBR · 2025
    Review
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13 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.

Wassim A BasheerFrom the Cedars-Sinai Heart Institute (W.A.B., S.X., I.E., Y.F., T.H., R.M.S.) and Department of Medicine (T.H., R.M.S.), Cedars-Sinai Medical Center and UCLA, Los Angeles, CA; and Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA (A.G.K.).
Shaohua XiaoFrom the Cedars-Sinai Heart Institute (W.A.B., S.X., I.E., Y.F., T.H., R.M.S.) and Department of Medicine (T.H., R.M.S.), Cedars-Sinai Medical Center and UCLA, Los Angeles, CA; and Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA (A.G.K.).
Irina EpifantsevaFrom the Cedars-Sinai Heart Institute (W.A.B., S.X., I.E., Y.F., T.H., R.M.S.) and Department of Medicine (T.H., R.M.S.), Cedars-Sinai Medical Center and UCLA, Los Angeles, CA; and Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA (A.G.K.).
Ying FuFrom the Cedars-Sinai Heart Institute (W.A.B., S.X., I.E., Y.F., T.H., R.M.S.) and Department of Medicine (T.H., R.M.S.), Cedars-Sinai Medical Center and UCLA, Los Angeles, CA; and Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA (A.G.K.).
Andre G KleberFrom the Cedars-Sinai Heart Institute (W.A.B., S.X., I.E., Y.F., T.H., R.M.S.) and Department of Medicine (T.H., R.M.S.), Cedars-Sinai Medical Center and UCLA, Los Angeles, CA; and Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA (A.G.K.).
TingTing HongFrom the Cedars-Sinai Heart Institute (W.A.B., S.X., I.E., Y.F., T.H., R.M.S.) and Department of Medicine (T.H., R.M.S.), Cedars-Sinai Medical Center and UCLA, Los Angeles, CA; and Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA (A.G.K.).
Robin M ShawFrom the Cedars-Sinai Heart Institute (W.A.B., S.X., I.E., Y.F., T.H., R.M.S.) and Department of Medicine (T.H., R.M.S.), Cedars-Sinai Medical Center and UCLA, Los Angeles, CA; and Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA (A.G.K.). robin.shaw@cshs.org.
Cedars-Sinai Medical Center · US

Funding

Novel Mechanisms of Cardiac Ion Channel RegulationR01HL094414 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI SHAW, ROBIN M · 2009 to 2018
$3.6M
Regulation of Ion Channels at BIN1-induced T-tubule MicrodomainsR01HL133286 · NHLBI · UNIVERSITY OF UTAH · PI HONG, TINGTING · 2016 to 2020
$2.2M
A New Non-Canonical Role for an Alternatively Translated Ion Channel ProteinR01HL138577 · NHLBI · UNIVERSITY OF UTAH · PI SHAW, ROBIN M · 2017 to 2020
$2.1M
NHLBI NIH HHS R01 HL094414NHLBI NIH HHS R01 HL133286NHLBI NIH HHS R01 HL138577
6 · The paper itself

Abstract

rationaleDelivery of Cx43 (connexin 43) to the intercalated disc is a continuous and rapid process critical for intercellular coupling. By a pathway of targeted delivery involving microtubule highways, vesicles of Cx43 hemichannels are efficiently trafficked to adherens junctions at intercalated discs. It has also been identified that actin provides rest stops for Cx43 forward trafficking and that Cx43 has a 20 kDa internally translated small C terminus isoform, GJA1-20k (Gap Junction Protein Alpha 1- 20 kDa), which is required for full-length Cx43 trafficking, but by an unknown mechanism.

objectiveWe explored the mechanism by which the GJA1-20k isoform is required for full-length Cx43 forward trafficking to intercalated discs. METHODS AND

resultsUsing an in vivo Adeno-associated virus serotype 9-mediated gene transfer system, we confirmed in whole animal that GJA1-20k markedly increases endogenous myocardial Cx43 gap junction plaque size at the intercalated discs. In micropatterned cell pairing systems, we found that exogenous GJA1-20k expression stabilizes filamentous actin without affecting actin protein expression and that GJA1-20k complexes with both actin and tubulin. We also found that filamentous actin regulates microtubule organization as inhibition of actin polymerization with a low dose of latrunculin A disrupts the targeting of microtubules to cell-cell junctions. GJA1-20k protects actin filament from latrunculin A disruption, preserving microtubule trajectory to the cell-cell border. For therapeutic implications, we found that prior in vivo Adeno-associated virus serotype 9-mediated gene delivery of GJA1-20k to the heart protects Cx43 localization to the intercalated discs against acute ischemic injury.

conclusionsThe internally translated GJA1-20k isoform stabilizes actin filaments, which guides growth trajectories of the Cx43 microtubule trafficking machinery, increasing delivery of Cx43 hemichannels to cardiac intercalated discs. Exogenous GJA1-20k helps to maintain cell-cell coupling in instances of anticipated myocardial ischemia.

Indexed as

Gene Transfer TechniquesActinsAnimalsAnimals, NewbornCells, CulturedConnexin 43HeLa CellsHumansMaleMiceMice, Inbred C57BLMicrotubulesMyocytes, CardiacOrgan Culture TechniquesProtein IsoformsProtein TransportActinsConnexin 43GJA1 protein, humanProtein Isoformsadherens junctionsconnexin 43cytoskeletongap junctionslatrunculin Atraffickingtubulin

Identifiers

PMID28923791
PMCPMC5790189
OpenAlexW2893248496

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.