C53 Interacting with UFM1-Protein Ligase 1 Regulates Microtubule Nucleation in Response to ER Stress
Anastasiya Klebanovych,
Stanislav Vinopal,
Eduarda Dráberová,
Vladimíra Sládková,
Tetyana Sulimenko,
Vadym Sulimenko,
Věra Vosecká,
Libor Macůrek,
Agustin Legido,
Pavel Dráber
Affiliations
Anastasiya Klebanovych
Laboratory of Biology of Cytoskeleton, Institute of Molecular Genetics of the Czech Academy of Sciences, CZ 142 20 Prague, Czech Republic
Stanislav Vinopal
Laboratory of Biology of Cytoskeleton, Institute of Molecular Genetics of the Czech Academy of Sciences, CZ 142 20 Prague, Czech Republic
Eduarda Dráberová
Laboratory of Biology of Cytoskeleton, Institute of Molecular Genetics of the Czech Academy of Sciences, CZ 142 20 Prague, Czech Republic
Vladimíra Sládková
Laboratory of Biology of Cytoskeleton, Institute of Molecular Genetics of the Czech Academy of Sciences, CZ 142 20 Prague, Czech Republic
Tetyana Sulimenko
Laboratory of Biology of Cytoskeleton, Institute of Molecular Genetics of the Czech Academy of Sciences, CZ 142 20 Prague, Czech Republic
Vadym Sulimenko
Laboratory of Biology of Cytoskeleton, Institute of Molecular Genetics of the Czech Academy of Sciences, CZ 142 20 Prague, Czech Republic
Věra Vosecká
Laboratory of Biology of Cytoskeleton, Institute of Molecular Genetics of the Czech Academy of Sciences, CZ 142 20 Prague, Czech Republic
Libor Macůrek
Laboratory of Biology of Cytoskeleton, Institute of Molecular Genetics of the Czech Academy of Sciences, CZ 142 20 Prague, Czech Republic
Agustin Legido
Section of Neurology, St. Christopher’s Hospital for Children, Department of Pediatrics, Drexel University College of Medicine, Philadelphia, PA 19134, USA
Pavel Dráber
Laboratory of Biology of Cytoskeleton, Institute of Molecular Genetics of the Czech Academy of Sciences, CZ 142 20 Prague, Czech Republic
ER distribution depends on microtubules, and ER homeostasis disturbance activates the unfolded protein response resulting in ER remodeling. CDK5RAP3 (C53) implicated in various signaling pathways interacts with UFM1-protein ligase 1 (UFL1), which mediates the ufmylation of proteins in response to ER stress. Here we find that UFL1 and C53 associate with γ-tubulin ring complex proteins. Knockout of UFL1 or C53 in human osteosarcoma cells induces ER stress and boosts centrosomal microtubule nucleation accompanied by γ-tubulin accumulation, microtubule formation, and ER expansion. C53, which is stabilized by UFL1, associates with the centrosome and rescues microtubule nucleation in cells lacking UFL1. Pharmacological induction of ER stress by tunicamycin also leads to increased microtubule nucleation and ER expansion. Furthermore, tunicamycin suppresses the association of C53 with the centrosome. These findings point to a novel mechanism for the relief of ER stress by stimulation of centrosomal microtubule nucleation.
