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Ena/VASP clustering at microspike tips involves lamellipodin but not I-BAR proteins, and absolutely requires unconventional myosin-X.
Pokrant, Thomas; Hein, Jens Ingo; Körber, Sarah; Disanza, Andrea; Pich, Andreas; Scita, Giorgio; Rottner, Klemens; Faix, Jan.
Affiliation
  • Pokrant T; Institute for Biophysical Chemistry, Hannover Medical School, 30625 Hannover, Germany.
  • Hein JI; Institute for Biophysical Chemistry, Hannover Medical School, 30625 Hannover, Germany.
  • Körber S; Institute for Biophysical Chemistry, Hannover Medical School, 30625 Hannover, Germany.
  • Disanza A; IFOM ETS (Istituto Fondazione di Oncologia Molecolare ETS),  - The AIRC (Italian Association for Cancer Research) Institute of Molecular Oncology, 20139 Milan, Italy.
  • Pich A; Research Core Unit Proteomics, Hannover Medical School, 30625 Hannover, Germany.
  • Scita G; IFOM ETS (Istituto Fondazione di Oncologia Molecolare ETS),  - The AIRC (Italian Association for Cancer Research) Institute of Molecular Oncology, 20139 Milan, Italy.
  • Rottner K; Department of Oncology and Haemato-Oncology, University of Milan, 20139 Milan, Italy.
  • Faix J; Division of Molecular Cell Biology, Zoological Institute, Technische Universität Braunschweig, 38106 Braunschweig, Germany.
Proc Natl Acad Sci U S A ; 120(2): e2217437120, 2023 01 10.
Article in En | MEDLINE | ID: mdl-36598940
ABSTRACT
Sheet-like membrane protrusions at the leading edge, termed lamellipodia, drive 2D-cell migration using active actin polymerization. Microspikes comprise actin-filament bundles embedded within lamellipodia, but the molecular mechanisms driving their formation and their potential functional relevance have remained elusive. Microspike formation requires the specific activity of clustered Ena/VASP proteins at their tips to enable processive actin assembly in the presence of capping protein, but the factors and mechanisms mediating Ena/VASP clustering are poorly understood. Systematic analyses of B16-F1 melanoma mutants lacking potential candidate proteins revealed that neither inverse BAR-domain proteins, nor lamellipodin or Abi is essential for clustering, although they differentially contribute to lamellipodial VASP accumulation. In contrast, unconventional myosin-X (MyoX) identified here as proximal to VASP was obligatory for Ena/VASP clustering and microspike formation. Interestingly, and despite the invariable distribution of other relevant marker proteins, the width of lamellipodia in MyoX-KO mutants was significantly reduced as compared with B16-F1 control, suggesting that microspikes contribute to lamellipodium stability. Consistently, MyoX removal caused marked defects in protrusion and random 2D-cell migration. Strikingly, Ena/VASP-deficiency also uncoupled MyoX cluster dynamics from actin assembly in lamellipodia, establishing their tight functional association in microspike formation.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Actins / Synapsins Type of study: Prognostic_studies Limits: Animals Language: En Journal: Proc Natl Acad Sci U S A Year: 2023 Document type: Article Affiliation country: Alemania

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Actins / Synapsins Type of study: Prognostic_studies Limits: Animals Language: En Journal: Proc Natl Acad Sci U S A Year: 2023 Document type: Article Affiliation country: Alemania