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, Steven G. Thomas and Neil V. Morgan
Received Date: 24th October 19
In specialised cells, the expression of specific tubulin isoforms and their subsequent post-translational modifications drive and co-ordinate unique morphologies and behaviours. The mechanisms by which β1 tubulin, the platelet and megakaryocyte lineage restricted tubulin isoform, drives platelet production and function remains poorly understood. We investigated the roles of two key post-translational polymodifications (polyglutamylation and polyglycylation) on these processes using a cohort of thrombocytopenic patients, human induced pluripotent stem cell (iPSC) derived megakaryocytes, and healthy human donor platelets. We find distinct patterns of polymodification in megakaryocytes and platelets, mediated by the cell specific expression of effecting (Tubulin Tyrosine Ligase Like - TTLL) and reversing (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.
Read in full at bioRxiv.
This is an abstract of a preprint hosted on an independent third party site. It has not been peer reviewed but is currently under consideration at Nature Communications.