EB1 directly regulates APC-mediated actin nucleation

M.Angeles Juanes, C Fees, G J Hoeprich, R Jaiswal, B L Goode

Research output: Contribution to journalArticle

Abstract

EB1 was discovered 25 years ago as a binding partner of the tumor suppressor Adenomatous Polyposis Coli (APC) [1]; however, the significance of EB1-APC interactions has remained poorly understood. EB1 functions at the center of a network of microtubule end-tracking proteins (+TIPs) [2–5], and APC binding to EB1 promotes EB1 association with microtubule ends and microtubule stabilization [6, 7]. Whether or not EB1 interactions govern functions of APC beyond microtubule regulation has not been explored. The C-terminal Basic domain of APC (APC-B) directly nucleates actin assembly, and this activity is required in vivo for directed cell migration and for maintaining normal levels of F-actin [8–10]. Although this region of APC is not required for tumor-suppressor activity [11], it is required for proper development and other biological functions [12–14]. Here, we show that EB1 binds APC-B and inhibits its actin nucleation function by blocking actin monomer recruitment. Consistent with these biochemical observations, knocking down EB1 increases F-actin levels in cells, and this can be rescued by disrupting APC-mediated actin nucleation. Conversely, overexpressing EB1 decreases F-actin levels and impairs directed cell migration, without altering microtubule organization and independent of its direct binding interactions with microtubules. Overall, our results define a new function for EB1 in negatively regulating APC-mediated actin assembly. Combining these findings with other recent studies showing that APC interactions regulate EB1-dependent effects on microtubule dynamics [7], we propose that EB1-APC interactions govern bidirectional cytoskeletal crosstalk by coordinating microtubule and actin dynamics.
Original languageEnglish
JournalCurrent Biology
Publication statusPublished - 2020

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    Juanes, M. A., Fees, C., Hoeprich, G. J., Jaiswal, R., & Goode, B. L. (2020). EB1 directly regulates APC-mediated actin nucleation. Current Biology.