A new class of cyclin dependent kinase in Chlamydomonas is required for coupling cell size to cell division.

Yubing Li,James G Umen,Bradley Jsc Olson,Cristina López-Paz,Dianyi Liu

doi:10.7554/elife.10767

Abstract

Proliferating cells actively control their size by mechanisms that are poorly understood. The unicellular green alga Chlamydomonas reinhardtii divides by multiple fission, wherein a 'counting' mechanism couples mother cell-size to cell division number allowing production of uniform-sized daughters. We identified a sizer protein, CDKG1, that acts through the retinoblastoma (RB) tumor suppressor pathway as a D-cyclin-dependent RB kinase to regulate mitotic counting. Loss of CDKG1 leads to fewer mitotic divisions and large daughters, while mis-expression of CDKG1 causes supernumerous mitotic divisions and small daughters. The concentration of nuclear-localized CDKG1 in pre-mitotic cells is set by mother cell size, and its progressive dilution and degradation with each round of cell division may provide a link between mother cell-size and mitotic division number. Cell-size-dependent accumulation of limiting cell cycle regulators such as CDKG1 is a potentially general mechanism for size control.

Highlights

Active maintenance of cell size has been observed across eukaryotic taxa (Jorgensen and Tyers, 2004; Tzur et al, 2009; Umen, 2005), yet the molecular bases for eukaryotic cell-size homeostasis have not been extensively investigated outside of fungi
CDKG1 was previously annotated as a Chlamydomonas-specific cyclin dependent kinase (Bisova et al, 2005), and for the remainder of this work we refer to the two insertion alleles as cdkg1-1 and cdkg1-2
We have made use of the uniquely accessible mitotic size control pathway of Chlamydomonas reinhardtii to identify a new cell-size regulator, CDKG1, whose activity enables mother cells to execute the correct number of mitotic cell divisions according to mother cell-size

Summary

Introduction

Active maintenance of cell size has been observed across eukaryotic taxa (Jorgensen and Tyers, 2004; Tzur et al, 2009; Umen, 2005), yet the molecular bases for eukaryotic cell-size homeostasis have not been extensively investigated outside of fungi. No consensus exists for the mechanisms underlying cell size control in budding yeast, though several molecular pathways have been found to impact cell size These include a regulatory loop involving accumulation of G1 cyclins and the removal of the inhibitory protein Whi5p from the transcriptional activator SBF that controls S phase entry (Costanzo et al, 2004; de Bruin et al, 2004; Di Talia et al, 2009; Liu et al, 2015; Schmoller et al, 2015). Budding yeast cell size control is influenced by ribosome biogenesis that acts to modulate growth rate and the critical size at which cells enter S-phase (Bernstein et al, 2007; Gomez-Herreros et al, 2013; Jorgensen et al, 2004). It was proposed that cell size is controlled by polar localization of the kinase Pom that establishes an inhibitory gradient which blocks

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