Mesenchymal Cell Invasion Requires Cooperative Regulation of Persistent Microtubule Growth by SLAIN2 and CLASP1

Benjamin P. Bouchet, Ivar Noordstra, Miranda van Amersfoort, Eugene A. Katrukha, York Christoph Ammon, Natalie D. ter Hoeve, Louis Hodgson, Marileen Dogterom, Patrick W.B. Derksen, Anna Akhmanova

Research output: Contribution to journalArticlepeer-review

31 Scopus citations

Abstract

Microtubules regulate signaling, trafficking, and cell mechanics, but the respective contribution of these functions to cell morphogenesis and migration in 3D matrices is unclear. Here, we report that the microtubule plus-end tracking protein (+TIP) SLAIN2, which suppresses catastrophes, is not required for 2D cell migration but is essential for mesenchymal cell invasion in 3D culture and in a mouse cancer model. We show that SLAIN2 inactivation does not affect Rho GTPase activity, trafficking, and focal adhesion formation. However, SLAIN2-dependent catastrophe inhibition determines microtubule resistance to compression and pseudopod elongation. Another +TIP, CLASP1, is also needed to form invasive pseudopods because it prevents catastrophes specifically at their tips. When microtubule growth persistence is reduced, inhibition of depolymerization is sufficient for pseudopod maintenance but not remodeling. We propose that catastrophe inhibition by SLAIN2 and CLASP1 supports mesenchymal cell shape in soft 3D matrices by enabling microtubules to perform a load-bearing function.

Original languageEnglish (US)
Pages (from-to)708-723
Number of pages16
JournalDevelopmental cell
Volume39
Issue number6
DOIs
StatePublished - Dec 19 2016

Keywords

  • +TIPs
  • 3D matrix
  • CLIP-170
  • EB1
  • Rab6
  • Rho GTPase
  • cell migration
  • ch-TOG
  • modeling
  • tumor invasion

ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Developmental Biology
  • Cell Biology

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