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bioRxiv · 10.1101/377879

Filopodome mapping identifies p130Cas as a mechanosensitive regulator of filopodia stability

Jacquemet, G.·Saup, R.·Hamidi, H.·Miihkinen, M.·Ivaska, J.
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Abstract

Filopodia are adhesive cellular protrusions specialised in the detection of extracellular matrix (ECM)-derived cues. While ECM engagement at focal adhesions is known to trigger the recruitment of hundreds of proteins (\"adhesome\") to fine-tune cellular behaviour, the components of the filopodia adhesions remain undefined. Here, we performed a structured illumination microscopy-based screen to map the localisation of 80 target proteins, linked to cell adhesion and migration, within filopodia. We demonstrate preferential enrichment of several adhesion proteins to either filopodia tips, filopodia shafts, or shaft subdomains suggesting divergent, spatially restricted functions for these proteins. Moreover, proteins with phospho-inositide (PI) binding sites are particularly enriched in filopodia. This, together with the strong localisation of PI(3,4)P2 in filopodia tips, predicts critical roles for PIs in regulating filopodia ultra-structure and function. Our mapping further reveals that filopodia adhesions consist of a unique set of proteins, the filopodome, that are distinct from classical nascent adhesions, focal adhesions and fibrillar adhesions. Using live imaging, we observe that filopodia adhesions can give rise to nascent adhesions, which, in turn, form focal adhesions. Finally, we demonstrate that p130Cas (BCAR1) is recruited to filopodia tips via its CCHD domain and acts as a mechanosensitive regulator of filopodia stability.

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Jacquemet, G., Saup, R., Hamidi, H., Miihkinen, M., Ivaska, J.. 2018-07-26. Filopodome mapping identifies p130Cas as a mechanosensitive regulator of filopodia stability. https://doi.org/10.1101/377879

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