TACC3 Regulates Microtubule Plus-End Dynamics and Cargo Transport in Interphase Cells

• Main Authors: Colleen Furey, Vladimir Jovasevic, Derek Walsh
• Format: Article
• Language: English
• Published: Elsevier 2020-01-01
• Series: Cell Reports
• Online Access: http://www.sciencedirect.com/science/article/pii/S2211124719316754

Summary: End-binding proteins (EBs) are widely viewed as master regulators of microtubule dynamics and function. Here, we show that while EB1 mediates the dynamic microtubule capture of herpes simplex virus type 1 (HSV-1) in fibroblasts, in neuronal cells, infection occurs independently of EBs through stable microtubules. Prompted by this, we find that transforming acid coiled-coil protein 3 (TACC3), widely studied in mitotic spindle formation, regulates the cytoplasmic localization of the microtubule polymerizing factor chTOG and influences microtubule plus-end dynamics during interphase to control infection in distinct cell types. Furthermore, perturbing TACC3 function in neuronal cells resulted in the formation of disorganized stable, detyrosinated microtubule networks and changes in cellular morphology, as well as impaired trafficking of both HSV-1 and transferrin. These trafficking defects in TACC3-depleted cells were reversed by the depletion of kinesin-1 heavy chains. As such, TACC3 is a critical regulator of interphase microtubule dynamics and stability that influences kinesin-1-based cargo trafficking. : While EB proteins are widely studied as master regulators of microtubule plus-end dynamics, Furey et al. report EB-independent regulation of microtubule arrays and cargo trafficking by the transforming acid coiled-coil-containing protein, TACC3. By controlling the formation of detyrosinated stable microtubule networks, TACC3 influences kinesin-1-based sorting of both host and pathogenic cargoes. Keywords: TACC3, microtubules, +TIP, cargo transport, virus