PT - JOURNAL ARTICLE AU - Verma, Vikash AU - Maresca, Thomas J. TI - Microtubule plus-tips act as signaling hubs for positioning the cleavage furrow during cytokinesis AID - 10.1101/339119 DP - 2018 Jan 01 TA - bioRxiv PG - 339119 4099 - http://biorxiv.org/content/early/2018/06/07/339119.short 4100 - http://biorxiv.org/content/early/2018/06/07/339119.full AB - Cell division in animal cells culminates with the formation of a contractile ring that divides the cytosol through formation of a cleavage furrow. Microtubules (MTs) are essential for furrow positioning, but the molecular nature of MT-derived spatial signals is unresolved. In this study essential cytokinesis regulators (the centralspindlin complex, aurora B kinase (ABK), and polo kinase) were visualized in Drosophila melanogaster (Dm) cells and found localize to and track MT plus-ends during cytokinesis. The RhoA GEF Pebble (Dm ECT2) did not robustly tip-track but became enriched at MT plus-tips rapidly following cortical contact resulting in RhoA activation and enrichment of myosin-regulatory light chain. Abrogation of cytokinesis regulator tip-tracking by EB1 depletion or deletion of a novel EB1-interaction motif (hxxPTxh) in the centralspindlin component RacGAP50C resulted in higher incidences of cytokinesis failure. We propose that EB1-dependent, MT plus-tip-based signaling hubs recruit cortical Dm ECT2 upon contact to locally activate RhoA.