Evidence map›Paper›PMID 26096974›Full record

ArticleCurrent biology : CB2015

WHAMM Directs the Arp2/3 Complex to the ER for Autophagosome Biogenesis through an Actin Comet Tail Mechanism.

David J Kast, Allison L Zajac, Erika L F Holzbaur, E Michael Ostap, Roberto Dominguez

Open access · bronzeAbstract read
In one paragraph

Article in Current biology : CB, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 86 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
86citing papers in PubMed, 2 pooled it
7.6field-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

86 citing papers in PubMed, 2 syntheses or guidelines pooled it, 126 citations in OpenAlex.

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  17. bioRxiv : the preprint server for biology · 2024
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26 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

5 authors at 1 institution in 1 country.

David J KastDepartment of Physiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Allison L ZajacDepartment of Physiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Erika L F HolzbaurDepartment of Physiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
E Michael OstapDepartment of Physiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Roberto DominguezDepartment of Physiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: droberto@mail.med.upenn.edu.
University of Pennsylvania · US

Funding

Role of Myosin-l in Membrane Dynamics and TransportP01GM087253 · NIGMS · UNIVERSITY OF PENNSYLVANIA · PI HOLZBAUR, ERIKA L · 2009 to 2018
$15.3M
BAR PROTEINS LINKING MEMBRANE AND CYTOSKELETON DYNAMICSR01MH087950 · NIMH · UNIVERSITY OF PENNSYLVANIA · PI DOMINGUEZ, ROBERTO · 2010 to 2020
$4.0M
NIGMS NIH HHS P01 GM087253NIMH NIH HHS R01 MH087950
6 · The paper itself

Abstract

Nucleation-promoting factors (NPFs) control the spatio-temporal activity of Arp2/3 complex in cells]. Thus, WASP and the WAVE complex direct the formation of branched actin networks at the leading edge during cell motility and endo/exocytosis, whereas the WASH complex is involved in endosomal transport. Less understood are WHAMM and JMY, two NPFs with similar domain architecture. JMY is found in the nucleus and the cytosol and is involved in transcriptional regulation, cell motility, and trans-Golgi transport. WHAMM was reported to bind microtubules and to be involved in ER to cis-Golgi transport. Here, we show that WHAMM directs the activity of Arp2/3 complex for autophagosome biogenesis through an actin-comet tail motility mechanism. Macroautophagy--the process by which cytosolic material is engulfed into autophagosomes for degradation and/or recycling--was recently shown to involve actin, but the mechanism is unknown. We found that WHAMM forms puncta that colocalize and comigrate with the autophagy markers LC3, DFCP1, and p62 through a WHAMM-dependent actin-comet tail mechanism. Under starvation, WHAMM and actin are observed at the interface between neighboring autophagosomes, whose number and size increase with WHAMM expression. Interfering with actin polymerization, inhibiting Arp2/3 complex, knocking down WHAMM, or blocking its interaction with Arp2/3 complex through mutagenesis all inhibit comet tail formation and reduce the size and number of autophagosomes. Finally, JMY shows similar localization to WHAMM and could be involved in similar processes. These results reveal a link between Arp2/3-complex-dependent actin assembly and autophagy.

Indexed as

Models, MolecularActin-Related Protein 2-3 ComplexActinsAutophagyBridged Bicyclo Compounds, HeterocyclicCalnexinCell LineComet AssayDepsipeptidesDynamic Light ScatteringEndoplasmic ReticulumGreen Fluorescent ProteinsHumansLuminescent ProteinsMembrane ProteinsMicrotubule-Associated ProteinsActin-Related Protein 2-3 ComplexActinsBridged Bicyclo Compounds, HeterocyclicCalnexinDepsipeptidesGreen Fluorescent Proteinsjasplakinolidelatrunculin BLuminescent ProteinsMembrane ProteinsMicrotubule-Associated ProteinsNocodazoleRed Fluorescent ProteinSEC61B protein, humanSEC Translocation ChannelsThiazolidinesWHAMM protein, human

Identifiers

PMID26096974
PMCPMC4489997
OpenAlexW1779577685

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.