| First Author | Strassel C | Year | 2019 |
| Journal | Life Sci Alliance | Volume | 2 |
| Issue | 1 | PubMed ID | 30760556 |
| Mgi Jnum | J:286522 | Mgi Id | MGI:6391839 |
| Doi | 10.26508/lsa.201900309 | Citation | Strassel C, et al. (2019) An essential role for alpha4A-tubulin in platelet biogenesis. Life Sci Alliance 2(1) |
| abstractText | 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 beta1-tubulin is known to be essential, no equivalent roles of alpha-tubulin isotypes in platelet formation or function have so far been reported. Here, we identify alpha4A-tubulin as a predominant alpha-tubulin isotype in platelets. Similar to beta1-tubulin, alpha4A-tubulin expression is up-regulated during the late stages of megakaryocyte differentiation. Missense mutations in the alpha4A-tubulin gene cause macrothrombocytopenia in mice and humans. Defects in alpha4A-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 Tuba4a-mutant mice. We have, thus, discovered an alpha-tubulin isotype with specific and essential roles in platelet biogenesis. |
