Talin Rod Domain Containing Protein 1 (TLNRD1) is a novel actin-bundling protein which promotes filopodia formation

Cowell, Alana ORCID: 0000-0003-4614-9364, Jacquemet, Guillaume ORCID: 0000-0002-9286-920X, Singh, Abhimanyu ORCID: 0000-0002-9998-020X, Ammon, York-Christoph, Brown, David, Akhmanova, Anna, Ivaska, Johanna and Goult, Benjamin ORCID: 0000-0002-3438-2807 (2020) Talin Rod Domain Containing Protein 1 (TLNRD1) is a novel actin-bundling protein which promotes filopodia formation. [Preprint]

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Official URL: http://dx.doi.org/10.1101/2020.05.19.103606

Abstract

Talin is a mechanosensitive adapter protein which couples integrins to the cytoskeleton and regulates integrin-mediated adhesion. Talin rod domain-containing protein-1 (TLNRD1) shares 22% homology with the R7R8 domains of talin, and is highly conserved throughout vertebrate evolution, however little is known about its function. Here we show that TLNRD1 is an α-helical protein which shares the same atypical topology as talin R7R8, but forms a novel antiparallel dimer arrangement. Actin co-sedimentation assays and electron microscopy reveal TLNRD1 is an actin-bundling protein that forms tight actin bundles. In addition, TLNRD1 binds to the same LD-motif containing proteins, RIAM and KANK, as talin, and thus may act in competition with talin. Filopodia are cell protrusions supported by tightly bundled actin filaments and TLNRD1 localises to filopodia tips, increases filopodia number and promotes cell migration in 2D. Together our results suggest that TLNRD1 has similar functionality to talin R7R8, serving as a nexus between the actin and microtubule cytoskeletons independent of adhesion complexes.

Item Type:	Preprint
Uncontrolled Keywords:	1 Underpinning research, 1.1 Normal biological development and functioning, Generic health relevance
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:	13 Mar 2024 09:59
Last Modified:	15 Mar 2024 20:51
DOI:	10.1101/2020.05.19.103606
Open Access URL:	https://doi.org/10.1101/2020.05.19.103606
Related URLs:	Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3179311