Evaluation of Striatin as a novel Microtubule Modulator

Abstract

The dynamics of the cell cycle and cell division are governed by tubulin polymers, <em>i. e.</em> microtubules (MTs). Defects of MT assembly or disassembly lead to pathogenic cellular conditions, negatively affecting cell viability, cell shape, migration and genomic stability. Previously, our lab established a screen for so far unknown mitotic and meiotic MT modulators. In this project, I distinguish, characterize and localize novel MT associated proteins (MAPs) and MT modulators, including Striatin (STRN). <br /> STRN is described as a regulating platform subunit in a kinase and phosphatase-harbouring complex called STRIPAK (Striatin phosphatase and kinase complex). A key component of this complex, Protein Phosphatase 2 A (PP2A), is known to play a major role in cell division progression also as MT dynamics regulator. In association with PP2A, STRN could function as a regulatory PP2A subunit for a tight posttranslational modification (PTM)-switch of yet unknown STRN interactors that function as MAPs. An interaction partner analysis by co-immunoprecipitation and binding partner analysis by mass spectrometry might address this question. <br /> Indeed, the STRN interactome in my work shows multiple partnerships to known MAPs. I further compare <em>in vivo</em> models, like the embryonic IMR-90 fibroblasts cell line with cell cycle-arrested <em>Xenopus leavis</em> egg extracts and find STRN-related similarities. I analyze the consequences of the lack of STRN in both models and in different cell cycle stages. STRN depletion in mitotic <em>Xenopus laevis</em> extracts stabilizes spindle structures. In human embryonic lung fibroblasts a CRISPR knock out (KO) of STRN decelerates mitotic progression and the cells stay longer in G₂/M-, pro- and especially in metaphase. Together with my results various facts suggest STRN has different roles in the cell regarding MT dynamics and ciliogenesis.