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A phosphorylation switch regulates RAB6 function during mitosis

Jimenez, A. J.; Bousquet, H.; Bardin, S.; Perez, F.; Goud, B.; Miserey, S.

2023-01-05 cell biology
10.1101/2023.01.05.522745 bioRxiv
Show abstract

RAB GTPases are key regulators of membrane trafficking in eukaryotic cells. In addition to their role in interphase, several RAB proteins, including Golgi-associated RAB6, have mitotic functions. The aim of this study was to investigate how the interphasic and mitotic functions of RAB6 could be regulated. Since phosphorylation is a key regulatory process in mitosis, we looked for specific mitotic phosphorylation of RAB6 using a phospho-proteomic approach. We found that RAB6 is phosphorylated at position S52 by the mitotic kinase Pololike kinase 1 (Plk1) in mitosis. Phosphorylated RAB6 localizes at the spindle poles from prophase to anaphase. In metaphase, we observed RAB6A-positive structures containing Mad1 and Mad2 moving along the mitotic spindle via the dynein-dynactin complex. We provide evidence that phosphorylation impairs RAB6A binding to some of its known partners, including p150Glued and Bicaudal-D2. In addition, the overexpression of RAB6A phospho-mutants lead to mitosis and cytokinesis defects. Our results suggest that a cycle of RAB6 phosphorylation/dephosphorylation is required for cell division.

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