Talin rod domain-containing protein 1 (TLNRD1) is a novel actin-bundling protein which promotes filopodia formation
Publication date
2021-09-06
Authors
Cowell, Alana R
Jacquemet, Guillaume
Singh, Abhimanyu K
Varela, Lorena
Nylund, Anna S
Ammon, York-Christoph
Brown, David G
Akhmanova, Anna
Ivaska, Johanna
Goult, Benjamin T
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Advisors
Supervisors
Document Type
Article
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Abstract
Talin is a mechanosensitive adapter protein that couples integrins to the cytoskeleton. Talin rod domain-containing protein 1 (TLNRD1) shares 22% homology with the talin R7R8 rod domains, and is highly conserved throughout vertebrate evolution, although little is known about its function. Here we show that TLNRD1 is an α-helical protein structurally homologous to talin R7R8. Like talin R7R8, TLNRD1 binds F-actin, but because it forms a novel antiparallel dimer, it also bundles F-actin. In addition, it binds the same LD motif-containing proteins, RIAM and KANK, as talin R7R8. In cells, TLNRD1 localizes to actin bundles as well as to filopodia. Increasing TLNRD1 expression enhances filopodia formation and cell migration on 2D substrates, while TLNRD1 down-regulation has the opposite effect. Together, our results suggest that TLNRD1 has retained the diverse interactions of talin R7R8, but has developed distinct functionality as an actin-bundling protein that promotes filopodia assembly.
Keywords
Actin Cytoskeleton/metabolism, Actins/genetics, Adaptor Proteins, Signal Transducing/genetics, Amino Acid Sequence, Binding Sites, Cell Line, Tumor, Cell Movement, Cloning, Molecular, Cytoskeletal Proteins/genetics, Escherichia coli/genetics, Gene Expression, Gene Expression Regulation, Genetic Vectors/chemistry, Humans, Membrane Proteins/genetics, Models, Molecular, Molecular Chaperones/antagonists & inhibitors, Osteoblasts/cytology, Protein Binding, Protein Conformation, alpha-Helical, Protein Multimerization, Pseudopodia/metabolism, RNA, Small Interfering/genetics, Recombinant Proteins/chemistry, Signal Transduction, Talin/genetics
Citation
Cowell, A R, Jacquemet, G, Singh, A K, Varela, L, Nylund, A S, Ammon, Y-C, Brown, D G, Akhmanova, A, Ivaska, J & Goult, B T 2021, 'Talin rod domain-containing protein 1 (TLNRD1) is a novel actin-bundling protein which promotes filopodia formation', Journal of Cell Biology, vol. 220, no. 9, e202005214. https://doi.org/10.1083/jcb.202005214