Optimized filopodia formation requires myosin tail domain cooperation

Ashley L. Arthur, Livia D. Songster, Helena Sirkia, Akash Bhattacharya, Carlos Kikuti, Fernanda Pires Borrega, Anne Houdusse, Margaret A. Titus

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Filopodia are actin-filled protrusions employed by cells to interact with their environment. Filopodia formation in Amoebozoa and Metazoa requires the phylogenetically diverse MyTH4-FERM (MF) myosins DdMyo7 and Myo10, respectively. While Myo10 is known to form antiparallel dimers, DdMyo7 lacks a coiled-coil domain in its proximal tail region, raising the question of how such divergent motors perform the same function. Here, it is shown that the DdMyo7 lever arm plays a role in both autoinhibition and function while the proximal tail region can mediate weak dimerization, and is proposed to be working in cooperation with the C-terminal MF domain to promote partner-mediated dimerization. Additionally, a forced dimer of the DdMyo7 motor is found to weakly rescue filopodia formation, further highlighting the importance of the C-terminal MF domain. Thus, weak dimerization activity of the DdMyo7 proximal tail allows for sensitive regulation of myosin activity to prevent inappropriate activation of filopodia formation. The results reveal that the principles of MF myosin-based filopodia formation are conserved via divergent mechanisms for dimerization.

Original languageEnglish (US)
Pages (from-to)22196-22204
Number of pages9
JournalProceedings of the National Academy of Sciences of the United States of America
Volume116
Issue number44
DOIs
StatePublished - Oct 29 2019

Bibliographical note

Funding Information:
LabexCelTisPhyBio:11-LBX-0038, which is part of the Initiatives of Excellence of Université Paris Sciences et Lettres (ANR-10-IDEX-0001-02PSL). Support was also provided by UMN’s Undergraduate Research Opportunities Program (L.D.S.) and grants from the UMN Medical Foundation, UMN Graduate School, the American Heart Association (to M.A.T.), and NIH National Institute of General Medical Sciences (F31GM128325 to A.L.A. and R01GM122917 to M.A.T.).

Funding Information:
comments on the manuscript; Dr. Karl Petersen and Himanshu Jain for development of the “Seven” FIJI script; Dr. Gant Luxton [University of Minnesota (UMN)] for use of the spinning disc confocal microscope; Dr. Ron Rock (University of Chicago) for kindly providing the Myo5 coiled-coil clone; and University Imaging Centers, UMN, for additional imaging support. The work was supported by the CNRS, ANR-17-CE11-0029-01, and Ligue Contre le Cancer RS16 grants (A.H.). The A.H. team is part of the

Publisher Copyright:
© 2019 National Academy of Sciences. All rights reserved.

Keywords

  • Actin
  • Filopodia
  • MyTH4-FERM
  • Myosin

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