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Spotlight Seminar - Maria Angeles Juanes : Crosstalk between cytoskeletal networks orchestrated by Adenomatous polyposis coli (APC) to promote directed cell migration.

When Dec 13, 2018
from 02:00 PM to 03:00 PM
Where Genetics Part II Room
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Spotlight Seminar Series

Maria Angeles Juanes will give a spotlight seminar at 2pm on Thursday 13 December in the Part II room.

Title: Crosstalk between cytoskeletal networks orchestrated by Adenomatous polyposis coli (APC) to promote directed cell migration.

Abstract: My research interests revolve around the mechanisms controlling cytoskeketal networks (particularly actin and microtubules) during cell division and polarity.  My studies began with budding yeast as a model but, in recent years I have explored integral cytoskeletal control during cell migration in mammalian cells. Actin and microtubules (MTs) are pivotal determinants supporting cell shape, motility and cell division. These polymer networks are shaped by hundreds of accessory proteins and associated regulatory proteins that control virtually every aspect of actin and MT dynamics resulting in an incredible range (in form and scale) of cellular structures. There is mounting evidence for a rich degree of functional crosstalk and physical linkage between the two systems, and their in vivo functions are closely intertwined. This is particularly apparent in the cycle of events underlying whole cell motility. Yet, the molecular bridges that connect both cytoskeletal systems have been mostly studied in the context of the individual polymers, separately. What is vitally needed now is a combinatorial approach to reveal the specific function of molecular mediators of actin-MT crosstalk.

The Adenomatous Polyposis Coli (APC) protein is an outstanding prototypical linker with the potential to integrate actin and microtubule functions. Indeed, APC is a multifunctional protein that binds to multiple molecular partners with established associations with either actin or MT cytoskeletal systems. APC is regarded as the 'gatekeeper' of colorectal cancer and plays critical roles in tissue morphogenesis and in brain development. For many years, APC was implicated in cell migration through its established roles in Wnt signalling and microtubule dynamics. However, APC also directly binds actin and promotes actin polymerization in vitro. To address the in vivo significance of APC's ties to actin, a separation-of-function mutant, APC-m4, that specifically abolishes actin nucleation by APC was generated. Using this mutant, we found that APC's actin nucleation activity is critical for focal adhesion turnover, and directed cell migration. Precise coordination between cell adhesion and migration is critical for development, morphogenesis, immune surveillance, tissue repair and has important implications in cancer progression. Future studies will allow us to dissect APC cytoskeletal contributions on cellular invasion and development as well as through potential crosstalk with the Wnt signalling pathway.