Inheritance of the Golgi Apparatus and Cytokinesis Are Controlled by Degradation of GBF1

Roberto Magliozzi,Zunamys I Carrero,Teck Yew Low,Laurensia Yuniati,Christian Valdes-Quezada,Flore Kruiswijk,Koen Van Wijk,Albert J.R Heck,Catherine L Jackson,Daniele Guardavaccaro

doi:10.1016/j.celrep.2018.05.031

Abstract

Although much is known about how chromosome segregation is coupled to cell division, how intracellular organelles partition during mitotic division is poorly understood. We report that the phosphorylation-dependent degradation of the ARFGEF GBF1 regulates organelle trafficking during cell division. We show that, in mitosis, GBF1 is phosphorylated on Ser292 and Ser297 by casein kinase-2 allowing recognition by the F-box protein βTrCP. GBF1 interaction with βTrCP recruits GBF1 to the SCFβTrCP ubiquitin ligase complex, triggering its degradation. Phosphorylation and degradation of GBF1 occur along microtubules at the intercellular bridge of telophase cells and are required for Golgi membranepositioning and postmitotic Golgi reformation. Indeed, expression of a non-degradable GBF1 mutant inhibits the transport of the Golgi cluster adjacent to the midbody toward the Golgi twin positioned next to the centrosome and results in defective Golgi reassembly and cytokinesis failure. These findings define a mechanism that controls postmitotic Golgi reassembly and inheritance.

Highlights

During cell division, chromosomes need to be distributed between daughter cells, and organelles have to be faithfully partitioned
We report that the phosphorylation-dependent degradation of the ARFGEF GBF1 regulates organelle trafficking during cell division
In mitosis, GBF1 is phosphorylated on Ser292 and Ser297 by casein kinase-2 allowing recognition by the F-box protein bTrCP

Summary

Introduction

Chromosomes need to be distributed between daughter cells, and organelles have to be faithfully partitioned. Continuous vesicle budding of the resulting single cisternae, and the concomitant inhibition of heterotypic and homotypic Golgi fusion events, lead to the formation of small tubulovesicular clusters in dynamic equilibrium with free vesicles and tubular remnants These clusters and vesicles disperse through the cytosol or, according to others, fuse to the endoplasmic reticulum (Shorter and Warren, 2002; Tang and Wang, 2013). The minor Golgi twin positioned next to the midbody gradually migrates to the other side of the nucleus and coalesces with the major Golgi twin, forming a single juxtanuclear Golgi ribbon (Gaietta et al, 2006) These elegant high-resolution livecell imaging techniques, combined with electron microscopy, have revealed how the Golgi apparatus reforms in late mitosis, the underlying molecular mechanisms remain elusive

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