TY - JOUR T1 - Dynactin binding to tyrosinated microtubules promotes centrosome centration in <em>C. elegans</em> by enhancing dynein-mediated organelle transport JF - bioRxiv DO - 10.1101/130104 SP - 130104 AU - Daniel José Barbosa AU - Joana Duro AU - Dhanya K. Cheerambathur AU - Bram Prevo AU - Ana Xavier Carvalho AU - Reto Gassmann Y1 - 2017/01/01 UR - http://biorxiv.org/content/early/2017/04/24/130104.abstract N2 - The microtubule-based motor dynein generates pulling forces for centrosome centration and mitotic spindle positioning in animal cells. How the essential dynein activator dynactin regulates these functions of the motor is incompletely understood. Here, we dissect the role of dynactin’s microtubule binding activity, located in p150’s CAP-Gly domain and an adjacent basic patch, in the C. elegans zygote. Using precise mutants engineered by genome editing, we show that microtubule tip tracking of dynein-dynactin is dispensable for targeting the motor to the cell cortex and for generating cortical pulling forces. Instead, p150 CAP-Gly mutants inhibit cytoplasmic pulling forces responsible for centration of centrosomes and attached pronuclei. The centration defects are mimicked by mutations of the C-terminal tyrosine of α-tubulin, and both p150 CAP-Gly and tubulin tyrosination mutants decrease the frequency of organelle transport from the cell periphery towards centrosomes during centration. In light of recent work on dynein-dynactin motility in vitro, our results suggest that p150 GAP-Gly domain binding to tyrosinated microtubules promotes initiation of dynein-mediated organelle transport in the dividing embryo, and that this function of dynactin is important for generating robust cytoplasmic pulling forces for centrosome centration. ER -