Arpin Regulates Migration Persistence by Interacting with Both Tankyrases and the Arp2/3 Complex

During cell migration, protrusion of the leading edge is driven by the polymerization of Arp2/3-dependent branched actin networks. Migration persistence is negatively regulated by the Arp2/3 inhibitory protein Arpin. To better understand Arpin regulation in the cell, we looked for its interacting pa...

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Bibliographic Details
Published in:International journal of molecular sciences 2021-04, Vol.22 (8), p.4115
Main Authors: Simanov, Gleb, Dang, Irene, Fokin, Artem I, Oguievetskaia, Ksenia, Campanacci, Valérie, Cherfils, Jacqueline, Gautreau, Alexis M
Format: Article
Language:English
Subjects:
Actin
Arp2/3
Arpin
Binding Sites
Carrier Proteins - chemistry
Carrier Proteins - metabolism
cell migration
Cell Movement
HEK293 Cells
HeLa Cells
Humans
Life Sciences
Liquid phases
migration persistence
Mutation
Phase separation
Phase transitions
Protein Binding
Proteins
Regulation
Tankyrase
Tankyrases - chemistry
Tankyrases - metabolism
Two-Hybrid System Techniques
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Summary:During cell migration, protrusion of the leading edge is driven by the polymerization of Arp2/3-dependent branched actin networks. Migration persistence is negatively regulated by the Arp2/3 inhibitory protein Arpin. To better understand Arpin regulation in the cell, we looked for its interacting partners and identified both Tankyrase 1 and 2 (TNKS) using a yeast two-hybrid screening and coimmunoprecipitation with full-length Arpin as bait. Arpin interacts with ankyrin repeats of TNKS through a C-terminal-binding site on its acidic tail, which overlaps with the Arp2/3-binding site. Arpin was found to dissolve the liquid-liquid phase separation of TNKS upon overexpression. To uncouple the interactions of Arpin with TNKS and Arp2/3, we introduced point mutations in the Arpin tail and attempted to rescue the increased migration persistence of the Arpin knockout cells using random plasmid integration or compensating knock-ins at the locus. Arpin mutations impairing interactions with either Arp2/3 or TNKS were insufficient to fully abolish Arpin activity. Only the mutation that affected both interactions rendered Arpin completely inactive, suggesting the existence of two independent pathways, whereby Arpin controls the migration persistence.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms22084115