Evidence map›Paper›PMID 22349696›Full record

ArticleJournal of cell science2012

Lysosome fusion to the cell membrane is mediated by the dysferlin C2A domain in coronary arterial endothelial cells.

Wei-Qing Han, Min Xia, Ming Xu, Krishna M Boini, Joseph K Ritter, Ning-Jun Li, Pin-Lan Li

Open access · greenAbstract read
In one paragraph

Article in Journal of cell science, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
3.6field-weighted citation impact, top 7% 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

25 citing papers in PubMed, 51 citations in OpenAlex.

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  11. Cellular mechanisms and signals that coordinate plasma membrane repair.Cellular and molecular life sciences : CMLS · 2018
    Review
  12. Article
  13. Article
  14. Coupling of excitation to CaThe Journal of physiology · 2017
    Article
  15. Article
  16. Article
  17. Article
  18. Ca2+ -regulated lysosome fusion mediates angiotensin II-induced lipid raft clustering in mesenteric endothelial cells.Hypertension research : official journal of the Japanese Society of Hypertension · 2016
    Article
  19. Article
  20. Article
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.

Wei-Qing HanDepartment of Pharmacology & Toxicology, Medical College of Virginia Campus, Virginia Commonwealth University, Richmond, VA 23298, USA.
Min Xia
Ming Xu
Krishna M Boini
Joseph K Ritter
Ning-Jun Li
Pin-Lan Li
Virginia Commonwealth University Medical Center · US

Funding

Regulation of Lysosomes in Autophagy in Coronary Arterial MyocytesR01HL057244 · NHLBI · VIRGINIA COMMONWEALTH UNIVERSITY · PI LI, PINLAN · 2001 to 2021
$6.7M
Subendothelial Exosomes in Coronary Microvascular DysfunctionR01HL075316 · NHLBI · VIRGINIA COMMONWEALTH UNIVERSITY · PI LI, PINLAN · 2004 to 2024
$6.7M
NAADP-Sensitive Lysosomal Ca2+ Release Channels-TRP-ML1 in Arterial MyocytesR01HL091464 · NHLBI · VIRGINIA COMMONWEALTH UNIVERSITY · PI LI, PINLAN · 2009 to 2013
$2.2M
Renal Medullary Stem Cell Niche in Salt Sensitive HypertensionR01HL106042 · NHLBI · VIRGINIA COMMONWEALTH UNIVERSITY · PI LI, NINGJUN · 2011 to 2014
$1.5M
MECHANISM OF CORONARY ENDOTHELIUM MEDIATED VASODILATIONR29HL057244 · NHLBI · MEDICAL COLLEGE OF WISCONSIN · PI LI, PIN-LAN · 1997 to 2000
$101k
NHLBI NIH HHS HL-091464NHLBI NIH HHS HL-57244NHLBI NIH HHS HL-75316NHLBI NIH HHS R01 HL057244NHLBI NIH HHS R01 HL075316NHLBI NIH HHS R01 HL091464NHLBI NIH HHS R01 HL106042NHLBI NIH HHS R29 HL057244
6 · The paper itself

Abstract

Dysferlin has recently been reported to participate in cell membrane repair in muscle and other cells through lysosome fusion. Given that lysosome fusion is a crucial mechanism that leads to membrane raft clustering, the present study attempted to determine whether dysferlin is involved in this process and its related signalling, and explores the mechanism underlying dysferlin-mediated lysosome fusion in bovine coronary arterial endothelial cells (CAECs). We found that dysferlin is clustered in membrane raft macrodomains after Fas Ligand (FasL) stimulation as detected by confocal microscopy and membrane fraction flotation. Small-interfering RNA targeted to dysferlin prevented membrane raft clustering. Furthermore, the translocation of acid sphingomyelinase (ASMase) to membrane raft clusters, whereby local ASMase activation and ceramide production--an important step that mediates membrane raft clustering--was attenuated. Functionally, silencing of the dysferlin gene reversed FasL-induced impairment of endothelium-dependent vasodilation in isolated small coronary arteries. By monitoring fluorescence quenching or dequenching, silencing of the dysferlin gene was found to almost completely block lysosome fusion to plasma membrane upon FasL stimulation. Further studies to block C2A binding and silencing of AHNAK (a dysferlin C2A domain binding partner), showed that the dysferlin C2A domain is required for FasL-induced lysosome fusion to the cell membrane, ASMase translocation and membrane raft clustering. We conclude that dysferlin determines lysosome fusion to the plasma membrane through its C2A domain and it is therefore implicated in membrane-raft-mediated signaling and regulation of endothelial function in coronary circulation.

Indexed as

AnimalsCattleCell MembraneCeramidesCoronary VesselsEndothelial CellsFas Ligand ProteinLysosomesMembrane MicrodomainsMembrane ProteinsMuscle ProteinsNADPH OxidasesPhosphatidylinositol PhosphatesProtein TransportRNA InterferenceRNA, Small InterferingCeramidesFas Ligand ProteinMembrane ProteinsMuscle ProteinsNADPH Oxidasesphosphatidylinositol 4-phosphatePhosphatidylinositol PhosphatesRNA, Small Interfering

Identifiers

PMID22349696
PMCPMC3324581
OpenAlexW2159273482

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.