TY - JOUR T1 - An essential role for α4A-tubulin in platelet biogenesis JF - Life Science Alliance JO - Life Sci. Alliance DO - 10.26508/lsa.201900309 VL - 2 IS - 1 SP - e201900309 AU - Catherine Strassel AU - Maria M Magiera AU - Arnaud Dupuis AU - Morgane Batzenschlager AU - Agnès Hovasse AU - Irina Pleines AU - Paul Guéguen AU - Anita Eckly AU - Sylvie Moog AU - Léa Mallo AU - Quentin Kimmerlin AU - Stéphane Chappaz AU - Jean-Marc Strub AU - Natarajan Kathiresan AU - Henri de la Salle AU - Alain Van Dorsselaer AU - Claude Ferec AU - Jean-Yves Py AU - Christian Gachet AU - Christine Schaeffer-Reiss AU - Benjamin T Kile AU - Carsten Janke AU - François Lanza Y1 - 2019/02/01 UR - https://www.life-science-alliance.org/content/2/1/e201900309.abstract N2 - 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 Tuba4a-mutant mice. We have, thus, discovered an α-tubulin isotype with specific and essential roles in platelet biogenesis. ER -