Actin-microtubule crosstalk by Adenomatous polyposis coli (APC) and EB1 in directed cell migration

Research output: Contribution to conferencePosterpeer-review

Abstract

Tight coordination between the microtubule and actin cytoskeletons is essential for a wide range of processes including directed cell migration. Molecules bridging both cytoskeletons mediate this coordination, but precise mechanisms remain unclear. The tumor supressor Adenomatous polyposis coli (APC) binds to both microtubules and actin. We generated a separation-of-function mutation in APC (APC-m4) which abolishes actin nucleation activity. Using this mutant tool, along with polarization-resolved microscopy, FRAP, super-resolution microscopy and live-cell TIRF-imaging we demonstrated that APC-mediated actin assembly is critical for normal levels, organization and dynamics of F-actin at focal adhesions (FAs), and proper organization of FA components. FAs are highly dynamic actin-based structures that assemble at the front of the cell and disassemble at the rear, allowing cells to move directionally. In adherent cells, microtubule ends are transiently captured at FAs, and deliver cargos that induce FA disassembly. We found that loss of APC-driven actin nucleation activity renders FAs less responsive to microtubule-induced disassembly, thus uncoupling the tight communication that normally exists between microtubules and FAs. As a result, APC-m4 cells presented disrupted cell migration. Biochemical assays showed that APC-mediated actin assembly activity is inhibited by the microtubule end-binding protein EB1. These observations correlate with EB1’s cellular effects on directed cell migration. Interestingly, APC and EB1 also localize at cell-cell junctions, suggesting that their interactions may extend to the remodeling of cell junctions in collective cell migration.
Original languageEnglish
Publication statusPublished - 14 Mar 2021
EventThe Dynamic Cell IV Conference: Biochemical Society and BSCB - Virtual
Duration: 14 Mar 202119 May 2021
Conference number: IV
https://www.eventsforce.net/biochemsoc/frontend/reg/thome.csp?pageID=51166&eventID=104&traceRedir=2

Conference

ConferenceThe Dynamic Cell IV Conference
Period14/03/2119/05/21
Internet address

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