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How to start a procentriole
Centrioles are crucial cellular organelles that form cores of centrosomes and cilia. Centrioles must replicate once every cell cycle producing exactly one daughter centriole. Both failure to replicate and production of supernumerary centrioles jeopardizes cellular life and can cause disease, such as microcephaly and cancer. Temporary regulation of centriole replication, which is provided by the cell cycle, has been largely elucidated. However, the numeric control that ensures that only one procentriole is produced by each pre-existing centriole remains an unsolved puzzle. In this talk I will present our theoretical model of the centriole initiation process. We postulate that a small module comprising a kinase PLK4 and its activator-substrate STIL/Ana2/SAS-5 is the core of the protein network responsible for the initiation of a procentriole. Our model recapitulates symmetry-breaking transition in the spatial localization of PLK4 from a symmetric ring surrounding mother centriole to a single spot marking the position of nascent procentriole. Importantly, our model predicts that induction of a single procentriole is not just an advantageous happenstance but the result of winner-takes-all competition between multiple centriolar loci for the PLK4-STIL complexes. Weakening of competition by overexpression of PLK4 and STIL causes progressive addition of supernumerary procentrioles, as has been observed experimentally.
Date:
13 February 2019, 11:00
Venue:
Sir William Dunn School of Pathology, South Parks Road OX1 3RE
Venue Details:
EPA Seminar Room
Speaker:
Prof Andrew Goryachev (Centre for Synthetic and Systems Biology, University of Edinburgh)
Organising department:
Sir William Dunn School of Pathology
Organiser:
Melissa Wright (Sir William Dunn School of Pathology)
Organiser contact email address:
melissa.wright@path.ox.ac.uk
Host:
Professor Jordan Raff (Sir William Dunn School of Pathology, University of Oxford)
Part of:
Dunn School of Pathology Research Seminars
Booking required?:
Not required
Audience:
Members of the University only
Editor:
Melissa Wright
