Abstract

SummaryERK1c is an alternatively spliced isoform of ERK1 that specifically regulates mitotic Golgi fragmentation, which allows division of the Golgi during mitosis. We have previously shown that ERK1c translocates to the Golgi during mitosis where it is activated by a resident MEK1b to induce Golgi fragmentation. However, the mechanism of ERK1c functions in the Golgi remained obscure. Here, we searched for ERK1c substrates and identified HOOK3 as a mediator of ERK1c-induced mitotic Golgi fragmentation, which requires a second phosphorylation by AuroraA for its function. In cycling cells, HOOK3 interacts with microtubules (MTs) and links them to the Golgi. Early in mitosis, HOOK3 is phosphorylated by ERK1c and later by AuroraA, resulting in HOOK3 detachment from the MTs, and elevated interaction with GM130. This detachment modulates Golgi stability and allows fragmentation of the Golgi. This study demonstrates a novel mechanism of Golgi apparatus destabilization early in mitosis to allow mitotic progression.

Highlights

  • Mitotic Golgi fragmentation is a central process in mammalian cells that allows division of the Golgi apparatus into the newly formed daughter cells, and allows proper mitotic progression (Ayala and Colanzi, 2017; Champion et al, 2017; Shorter and Warren, 2002)

  • We have previously shown that ERK1c translocates to the Golgi during mitosis where it is activated by a resident MEK1b to induce Golgi fragmentation

  • We searched for ERK1c substrates and identified HOOK3 as a mediator of ERK1cinduced mitotic Golgi fragmentation, which requires a second phosphorylation by AuroraA for its function

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Summary

Introduction

Mitotic Golgi fragmentation is a central process in mammalian cells that allows division of the Golgi apparatus into the newly formed daughter cells, and allows proper mitotic progression (Ayala and Colanzi, 2017; Champion et al, 2017; Shorter and Warren, 2002). The Golgi apparatus is organized into stacks of cisternae that are interconnected to form a ribbon-like structure, localized as a condensed structure adjacent to the nuclei (Makhoul et al, 2018) This structure is well known for its function in protein trafficking and post-translational modification of membranal or secreted proteins (McCaughey and Stephens, 2019). The second step is the dispersal of the stacks into thousands of small vesicles localized all over the mitotic cell, which occurs during prometaphase and lasts through anaphase Some of these vesicles may fuse to the ER or other membranes, but many of the vesicles remain dispersed within the cell (Ayala et al, 2020; Champion et al, 2017). Toward the end of mitosis (telophase), the small vesicles merge back together to form a full-size Golgi apparatus in each of the newly formed daughter cell

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