Evidence map›Paper›PMID 33893293›Full record

ArticleNature communications2021

Cdk5 and GSK3β inhibit fast endophilin-mediated endocytosis.

Antonio P A Ferreira, Alessandra Casamento, Sara Carrillo Roas, Els F Halff, James Panambalana, Shaan Subramaniam, Kira Schützenhofer, Laura Chan Wah Hak, Kieran McGourty, Konstantinos Thalassinos and 3 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed
3.3field-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

30 citing papers in PubMed, 44 citations in OpenAlex.

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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

13 authors at 7 institutions in 4 countries.

Antonio P A Ferreira *Institute of Structural and Molecular Biology, University College London, London, UK.ORCID 0000-0003-4614-8580
Alessandra Casamento *Institute of Structural and Molecular Biology, University College London, London, UK.ORCID 0000-0001-6156-9020
Sara Carrillo RoasInstitute of Structural and Molecular Biology, University College London, London, UK.ORCID 0000-0001-9956-1294
Els F HalffDepartment of Neuroscience, Physiology, and Pharmacology, University College London, London, UK.ORCID 0000-0001-5814-0899
James PanambalanaInstitute of Structural and Molecular Biology, University College London, London, UK.
Shaan SubramaniamInstitute of Structural and Molecular Biology, University College London, London, UK.
Kira SchützenhoferInstitute of Structural and Molecular Biology, University College London, London, UK.
Laura Chan Wah HakInstitute of Structural and Molecular Biology, University College London, London, UK.
Kieran McGourtyInstitute of Structural and Molecular Biology, University College London, London, UK.ORCID 0000-0003-1218-1833
Konstantinos ThalassinosInstitute of Structural and Molecular Biology, University College London, London, UK.
Josef T KittlerDepartment of Neuroscience, Physiology, and Pharmacology, University College London, London, UK.ORCID 0000-0002-3437-9456
Denis MartinvaletDepartment of Biochemistry, University of Padova, Padova, Italy.ORCID 0000-0002-6027-1270
Emmanuel BoucrotInstitute of Structural and Molecular Biology, University College London, London, UK. e.boucrot@ucl.ac.uk.ORCID 0000-0001-7312-6462
Institute of Structural and Molecular Biology · GBBrigham and Women's Hospital · USKing's College London · GBUniversity College London · GBUniversity of Limerick · IEUniversity of Oxford · GBUniversity of Padua · IT

Funding

Biotechnology and Biological Sciences Research Council BB/R01551XBiotechnology and Biological Sciences Research Council BB/R01552XMedical Research Council MR/N025644/1Wellcome TrustWellcome Trust 104913/Z/14/ZBM
6 · The paper itself

Abstract

Endocytosis mediates the cellular uptake of micronutrients and cell surface proteins. Fast Endophilin-mediated endocytosis, FEME, is not constitutively active but triggered upon receptor activation. High levels of growth factors induce spontaneous FEME, which can be suppressed upon serum starvation. This suggested a role for protein kinases in this growth factor receptor-mediated regulation. Using chemical and genetic inhibition, we find that Cdk5 and GSK3β are negative regulators of FEME. They antagonize the binding of Endophilin to Dynamin-1 and to CRMP4, a Plexin A1 adaptor. This control is required for proper axon elongation, branching and growth cone formation in hippocampal neurons. The kinases also block the recruitment of Dynein onto FEME carriers by Bin1. As GSK3β binds to Endophilin, it imposes a local regulation of FEME. Thus, Cdk5 and GSK3β are key regulators of FEME, licensing cells for rapid uptake by the pathway only when their activity is low.

Indexed as

Adaptor Proteins, Signal TransducingAnimalsCells, CulturedClathrinCyclin-Dependent Kinase 5Dynamin IEndocytosisGene Expression RegulationGlycogen Synthase Kinase 3 betaHEK293 CellsHeLa CellsHippocampusHumansMiceMice, Inbred C57BLMuscle ProteinsAdaptor Proteins, Signal TransducingClathrinCyclin-Dependent Kinase 5DPYSL3 protein, humanDynamin IGlycogen Synthase Kinase 3 betaMuscle ProteinsSH3GL2 protein, human

Identifiers

PMID33893293
PMCPMC8065113
OpenAlexW3152582992

What Socratic holds

Textmetadata
LicenceCC BY
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 Socratic graph.