Evidence map›Paper›PMID 33327716›Full record

ArticleHaematologica2022

Post-translational polymodification of β1-tubulin regulates motor protein localisation in platelet production and function.

Abdullah O Khan, Alexandre Slater, Annabel Maclachlan, Phillip L R Nicolson, Jeremy A Pike, Jasmeet S Reyat, Jack Yule, Rachel Stapley, Julie Rayes, Steven G Thomas and 1 more

Open access · goldAbstract read
In one paragraph

Article in Haematologica, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
2.5field-weighted citation impact, top 9% 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

17 citing papers in PubMed, 25 citations in OpenAlex.

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  17. Tubulin in Platelets: When the Shape Matters.International journal of molecular sciences · 2019
    Review
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

11 authors at 2 institutions in 1 country.

Abdullah O KhanInstitute of Cardiovascular Sciences, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham, UK, B15 2TT. a.khan.4@bham.ac.uk.
Alexandre SlaterInstitute of Cardiovascular Sciences, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham, UK, B15 2TT.
Annabel MaclachlanInstitute of Cardiovascular Sciences, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham, UK, B15 2TT.
Phillip L R NicolsonInstitute of Cardiovascular Sciences, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham, UK, B15 2TT.
Jeremy A PikeInstitute of Cardiovascular Sciences, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham, UK, B15 2TT; Centre of Membrane and Protein and Receptors (COMPARE), University of Birmingham and University of Nottingham, Midlands.
Jasmeet S ReyatInstitute of Cardiovascular Sciences, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham, UK, B15 2TT.
Jack YuleCentre of Membrane and Protein and Receptors (COMPARE), University of Birmingham and University of Nottingham, Midlands.
Rachel StapleyInstitute of Cardiovascular Sciences, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham, UK, B15 2TT.
Julie RayesInstitute of Cardiovascular Sciences, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham, UK, B15 2TT.
Steven G ThomasInstitute of Cardiovascular Sciences, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham, UK, B15 2TT; Centre of Membrane and Protein and Receptors (COMPARE), University of Birmingham and University of Nottingham, Midlands.
Neil V MorganInstitute of Cardiovascular Sciences, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham, UK, B15 2TT. N.V.Morgan@bham.ac.uk.
University of Birmingham · GBUniversity of Nottingham · GB

Funding

British Heart Foundation FS/13/70/30521British Heart Foundation FS/15/18/31317British Heart Foundation PG/13/36/30275British Heart Foundation PG/16/103/32650Wellcome Trust
6 · The paper itself

Abstract

In specialised cells, the expression of specific tubulin isoforms and their subsequent post-translational modifications drive and coordinate unique morphologies and behaviours. The mechanisms by which β1-tubulin, the platelet and megakaryocyte (MK) lineage restricted tubulin isoform, drives platelet production and function remains poorly understood. We investigated the roles of two key post-translational tubulin polymodifications (polyglutamylation and polyglycylation) on these processes using a cohort of thrombocytopenic patients, human induced pluripotent stem cell (iPSC) derived MKs, and healthy human donor platelets. We find distinct patterns of polymodification in MKs and platelets, mediated by the antagonistic activities of the cell specific expression of Tubulin Tyrosine Ligase Like (TTLLs) and Cytosolic Carboxypeptidase (CCP) enzymes. The resulting microtubule patterning spatially regulates motor proteins to drive proplatelet formation in megakaryocytes, and the cytoskeletal reorganisation required for thrombus formation. This work is the first to show a reversible system of polymodification by which different cell specific functions are achieved.

Indexed as

Induced Pluripotent Stem CellsTubulinBlood PlateletsHumansMegakaryocytesProtein Processing, Post-TranslationalThrombopoiesisTubulin

Identifiers

PMID33327716
PMCPMC8719104
OpenAlexW3111294001

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.