Myosin-X recruits lamellipodin to filopodia tips.

Popović, Ana, Miihkinen, Mitro, Ghimire, Sujan ORCID: 0000-0003-3660-4300, Saup, Rafael, Grönloh, Max LB, Ball, Neil J ORCID: 0000-0001-7165-6363, Goult, Benjamin T ORCID: 0000-0002-3438-2807, Ivaska, Johanna ORCID: 0000-0002-6295-6556 and Jacquemet, Guillaume ORCID: 0000-0002-9286-920X (2023) Myosin-X recruits lamellipodin to filopodia tips. Journal of cell science, 136 (5). jcs260574-.

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Official URL: http://dx.doi.org/10.1242/jcs.260574

Abstract

Myosin-X (MYO10), a molecular motor localizing to filopodia, is thought to transport various cargo to filopodia tips, modulating filopodia function. However, only a few MYO10 cargoes have been described. Here, using GFP-Trap and BioID approaches combined with mass spectrometry, we identified lamellipodin (RAPH1) as a novel MYO10 cargo. We report that the FERM domain of MYO10 is required for RAPH1 localization and accumulation at filopodia tips. Previous studies have mapped the RAPH1 interaction domain for adhesome components to its talin-binding and Ras-association domains. Surprisingly, we find that the RAPH1 MYO10-binding site is not within these domains. Instead, it comprises a conserved helix located just after the RAPH1 pleckstrin homology domain with previously unknown functions. Functionally, RAPH1 supports MYO10 filopodia formation and stability but is not required to activate integrins at filopodia tips. Taken together, our data indicate a feed-forward mechanism whereby MYO10 filopodia are positively regulated by MYO10-mediated transport of RAPH1 to the filopodium tip.

Item Type:	Article
Uncontrolled Keywords:	Pseudopodia, Myosins, Integrins, Binding Sites, Mass Spectrometry
Divisions:	Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology
Depositing User:	Symplectic Admin
Date Deposited:	04 Mar 2024 09:21
Last Modified:	04 Mar 2024 09:21
DOI:	10.1242/jcs.260574
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3179053