RT Journal Article
SR Electronic
T1 TAOK2 is an ER-localized Kinase that Catalyzes the Dynamic Tethering of ER to Microtubules
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.04.22.440958
DO 10.1101/2021.04.22.440958
A1 Kimya Nourbakhsh
A1 Amy A. Ferreccio
A1 Matthew J. Bernard
A1 Smita Yadav
YR 2021
UL http://biorxiv.org/content/early/2021/04/22/2021.04.22.440958.abstract
AB The endoplasmic reticulum (ER) depends on extensive association with the microtubule cytoskeleton for its structure, function and mitotic inheritance. The identity of molecular tethers that mediate ER-microtubule coupling, and mechanisms through which dynamic tethering is regulated are poorly understood. Here, we identify, Thousand And One amino acid Kinase 2 (TAOK2) as a pleiotropic protein kinase that mediates tethering of ER to microtubules. We show that TAOK2 is a unique multipass membrane spanning serine/threonine kinase localized in distinct ER domains via four transmembrane and amphipathic helices. Using in vitro and cellular assays, we find that TAOK2 directly binds microtubules with high affinity. We define the minimal TAOK2 determinants that induce ER-microtubule tethering, and delineate the mechanism for its autoregulation. While ER membrane dynamics are increased in TAOK2 knockout cells, the movement of ER along growing microtubule plus-ends is disrupted. We show that ER-microtubule tethering is tightly regulated by catalytic activity of TAOK2 in both interphase and mitotic cells, perturbation of which leads to profound defects in ER morphology and cell division. Our study identifies TAOK2 as an ER-microtubule tether, and reveals a kinase-regulated mechanism for control of ER dynamics critical for cell growth and division.Competing Interest StatementThe authors have declared no competing interest.