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TitleArpC5 isoforms regulate Arp2/3 complex-dependent protrusion through differential Ena/VASP positioning.
Journal, issue, pagesSci Adv, Vol. 9, Issue 3, Page eadd6495, Year 2023
Publish dateJan 20, 2023
AuthorsFlorian Fäßler / Manjunath G Javoor / Julia Datler / Hermann Döring / Florian W Hofer / Georgi Dimchev / Victor-Valentin Hodirnau / Jan Faix / Klemens Rottner / Florian K M Schur /
PubMed AbstractRegulation of the Arp2/3 complex is required for productive nucleation of branched actin networks. An emerging aspect of regulation is the incorporation of subunit isoforms into the Arp2/3 complex. ...Regulation of the Arp2/3 complex is required for productive nucleation of branched actin networks. An emerging aspect of regulation is the incorporation of subunit isoforms into the Arp2/3 complex. Specifically, both ArpC5 subunit isoforms, ArpC5 and ArpC5L, have been reported to fine-tune nucleation activity and branch junction stability. We have combined reverse genetics and cellular structural biology to describe how ArpC5 and ArpC5L differentially affect cell migration. Both define the structural stability of ArpC1 in branch junctions and, in turn, by determining protrusion characteristics, affect protein dynamics and actin network ultrastructure. ArpC5 isoforms also affect the positioning of members of the Ena/Vasodilator-stimulated phosphoprotein (VASP) family of actin filament elongators, which mediate ArpC5 isoform-specific effects on the actin assembly level. Our results suggest that ArpC5 and Ena/VASP proteins are part of a signaling pathway enhancing cell migration.
External linksSci Adv / PubMed:36662867 / PubMed Central
MethodsEM (subtomogram averaging) / EM (tomography)
Resolution7.8 - 8.1 Å
Structure data

EMDB-15136: In-cell structure of the actin filament Arp2/3 complex branch junction in lamellipodia of WT B16-F1 mouse melanoma cells
Method: EM (subtomogram averaging) / Resolution: 8.0 Å

EMDB-15137: Tomogram of a lamellipodium of a WT B16-F1 mouse melanoma cell
Method: EM (tomography)

EMDB-15138: In-cell structure of the actin filament Arp2/3 complex branch junction in lamellipodia of ArpC5 knockout B16-F1 mouse melanoma cells
Method: EM (subtomogram averaging) / Resolution: 8.1 Å

EMDB-15139: Tomogram of a lamellipodium of an ArpC5 knockout B16-F1 mouse melanoma cell
Method: EM (tomography)

EMDB-15140: In-cell structure of the actin filament Arp2/3 complex branch junction in lamellipodia of ArpC5L knockout B16-F1 mouse melanoma cells
Method: EM (subtomogram averaging) / Resolution: 7.8 Å

EMDB-15141: Tomogram of a lamellipodium of an ArpC5L knockout B16-F1 mouse melanoma cell
Method: EM (tomography)

Source
  • Mus musculus (house mouse)

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