The atypical protein kinase haspin is conserved in all eukaryotes and promotes the correct alignment of chromosomes on the metaphase plate by recruitment of the CPC. Here, using budding yeast as a model organism, we identified new functions for haspin paralogues (Alk1 and Alk2) in regulating actin and nuclear dynamics. Indeed, we show that haspin mutants experiencing mitotic delays accumulate actin and elongate their spindles entirely in daughter cells, with the consequence of generating anucleated mothers and binucleated daughters that are not vital. These defects are due to a hyperaccumulation of polarity proteins at the bud tip and indeed dispersion of these polarity factors or restoration of their physiological localization reduces the severity of the defects of haspin lacking cells. We also demonstrate that haspin regulates polarisome dispersion by affecting the distribution of Cdc42 activity in cells, particularly regulating the localization of Cdc24, the Cdc42 GEF. We report that localization of this GEF is regulated by Ras in mitosis and that haspin regulates the localization of Ras. We also noticed that loss of haspin causes a polarized delivery of exocytic vesicles towards the bud tip that could explain the defective localization of Ras in alk1∆alk2∆ cells. Moreover, we identified Fab1 kinase as a putative interactor of Alk2 and provide evidences for a interplay between haspin and Fab1 complex.
|Titolo:||HASPIN ROLE IN VESICLE DELIVERY AND POLARITY DISPERSION|
|Data di pubblicazione:||29-nov-2016|
|Settore Scientifico Disciplinare:||Settore BIO/11 - Biologia Molecolare|
|Citazione:||HASPIN ROLE IN VESICLE DELIVERY AND POLARITY DISPERSION / R. Quadri ; tutor: M. Muzi-Falconi. - Milano : Università degli studi di Milano. DIPARTIMENTO DI BIOSCIENZE, 2016 Nov 29. ((28. ciclo, Anno Accademico 2015.|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.13130/quadri-roberto_phd2016-11-29|
|Appare nelle tipologie:||Tesi di dottorato|