TAOK2 is an ER-localized kinase that catalyzes the dynamic tethering of ER to microtubules

The endoplasmic reticulum (ER) depends on extensive association with the microtubule (MT) cytoskeleton for its structure and mitotic inheritance. However, mechanisms that underlie coupling of ER membranes to MTs are poorly understood. We have identified thousand and one amino acid kinase 2 (TAOK2) as a pleiotropic protein kinase that mediates tethering of ER to MTs. In human cells, TAOK2 localizes in distinct ER subdomains via transmembrane helices and an adjacent amphipathic region. Through its C-terminal tail, TAOK2 directly binds MTs, coupling ER membranes to the MT cytoskeleton. In TAOK2 knockout cells, although ER-membrane dynamics are increased, movement of ER along growing MT plus ends is disrupted. ER-MT tethering is tightly regulated by catalytic activity of TAOK2, perturbation of which leads to defects in ER morphology, association with MTs, and cell division. Our study identifies TAOK2 as an ER-MT tether and reveals a kinase-regulated mechanism for control of ER dynamics.