An essential role for α4A-tubulin in platelet biogenesis.
Alkylating Agents
/ administration & dosage
Animals
Antigens, CD34
/ metabolism
Blood Platelets
/ physiology
Cells, Cultured
Ethylnitrosourea
/ administration & dosage
Humans
Male
Megakaryocytes
/ metabolism
Mice
Mice, Inbred BALB C
Microtubules
/ metabolism
Mutation, Missense
Platelet Count
Thrombocytopenia
/ genetics
Thrombopoiesis
/ physiology
Tissue Donors
Tubulin
/ genetics
Journal
Life science alliance
ISSN: 2575-1077
Titre abrégé: Life Sci Alliance
Pays: United States
ID NLM: 101728869
Informations de publication
Date de publication:
02 2019
02 2019
Historique:
received:
16
01
2019
revised:
23
01
2019
accepted:
23
01
2019
entrez:
15
2
2019
pubmed:
15
2
2019
medline:
15
2
2019
Statut:
epublish
Résumé
During platelet biogenesis, microtubules (MTs) are arranged into submembranous structures (the marginal band) that encircle the cell in a single plane. This unique MT array has no equivalent in any other mammalian cell, and the mechanisms responsible for this particular mode of assembly are not fully understood. One possibility is that platelet MTs are composed of a particular set of tubulin isotypes that carry specific posttranslational modifications. Although β1-tubulin is known to be essential, no equivalent roles of α-tubulin isotypes in platelet formation or function have so far been reported. Here, we identify α4A-tubulin as a predominant α-tubulin isotype in platelets. Similar to β1-tubulin, α4A-tubulin expression is up-regulated during the late stages of megakaryocyte differentiation. Missense mutations in the α4A-tubulin gene cause macrothrombocytopenia in mice and humans. Defects in α4A-tubulin lead to changes in tubulin tyrosination status of the platelet tubulin pool. Ultrastructural defects include reduced numbers and misarranged MT coils in the platelet marginal band. We further observed defects in megakaryocyte maturation and proplatelet formation in
Identifiants
pubmed: 30760556
pii: 2/1/e201900309
doi: 10.26508/lsa.201900309
pmc: PMC6374996
pii:
doi:
Substances chimiques
Alkylating Agents
0
Antigens, CD34
0
Tubulin
0
Ethylnitrosourea
P8M1T4190R
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Commentaires et corrections
Type : ErratumIn
Informations de copyright
© 2019 Strassel et al.
Références
Electrophoresis. 1997 Jan;18(1):127-35
pubmed: 9059834
EMBO J. 1988 Aug;7(8):2311-9
pubmed: 2461292
EMBO Mol Med. 2018 Dec;10(12):
pubmed: 30446499
J Biol Chem. 2006 May 12;281(19):13628-35
pubmed: 16554299
Cell Motil Cytoskeleton. 1993;25(1):19-29
pubmed: 8519065
Proc Natl Acad Sci U S A. 2005 May 31;102(22):7853-8
pubmed: 15899979
Am J Pathol. 1968 Aug;53(2):281-91
pubmed: 5667580
J Cell Biol. 2014 Aug 18;206(4):461-72
pubmed: 25135932
J Mol Biol. 1986 May 20;189(2):367-70
pubmed: 2427729
Am J Pathol. 1998 Feb;152(2):597-609
pubmed: 9466587
Methods Mol Biol. 2012;788:175-92
pubmed: 22130708
Methods Cell Biol. 2013;115:247-67
pubmed: 23973077
Cell Motil Cytoskeleton. 2003 Jul;55(3):213-20
pubmed: 12789665
Dev Cell. 2018 Oct 22;47(2):175-190.e5
pubmed: 30245156
Blood. 2008 May 1;111(9):4605-16
pubmed: 18230754
Methods Mol Biol. 2004;272:13-28
pubmed: 15226531
Blood. 2009 Jan 8;113(2):458-61
pubmed: 18849486
Blood. 2015 Jan 29;125(5):860-8
pubmed: 25411426
Curr Opin Hematol. 2016 Sep;23(5):486-92
pubmed: 27438527
Nat Cell Biol. 2017 Apr;19(4):391-398
pubmed: 28250419
Mol Cell Biol. 1986 Jul;6(7):2409-19
pubmed: 3785200
Nature. 1983 Oct 20-26;305(5936):738-40
pubmed: 6633643
Blood. 2016 May 5;127(18):2231-40
pubmed: 26966088
J Cell Sci. 1985 Oct;78:1-22
pubmed: 4093466
Ann Biol Clin (Paris). 2014 Sep-Oct;72(5):561-81
pubmed: 25336130
Platelets. 2017 Jan;28(1):3-13
pubmed: 27161842
Proteomics. 2012 Apr;12(8):1073
pubmed: 22577009
Exp Cell Res. 2012 Jan 1;318(1):25-32
pubmed: 22008103
Blood. 2012 Nov 15;120(20):4215-8
pubmed: 22955928
Blood. 2005 Dec 15;106(13):4076-85
pubmed: 16118321
Blood. 2003 Jun 15;101(12):4789-96
pubmed: 12586623
Blood. 2009 Apr 2;113(14):3182-9
pubmed: 18984861
Science. 2016 Apr 22;352(6284):aaf0659
pubmed: 27102488
Exp Hematol. 2012 Jul;40(7):564-74
pubmed: 22381681
Cell. 1987 Oct 23;51(2):283-92
pubmed: 2444342
Cell Host Microbe. 2012 May 17;11(5):515-27
pubmed: 22607804
Blood. 2000 Aug 15;96(4):1366-73
pubmed: 10942379
Nat Commun. 2017 Nov 27;8(1):1786
pubmed: 29176689
Curr Biol. 2001 Apr 17;11(8):579-86
pubmed: 11369202
J Cell Biol. 1986 Nov;103(5):1903-10
pubmed: 3782288
J Cell Biol. 1989 Aug;109(2):663-73
pubmed: 2503525