Activated I-BAR IRSp53 clustering controls the formation of VASP-actin-based membrane protrusions

Feng Ching Tsai, J. Michael Henderson, Zack Jarin, Elena Kremneva, Yosuke Senju, Julien Pernier, Oleg Mikhajlov, John Manzi, Konstantin Kogan, Christophe Le Clainche, Gregory A. Voth, Pekka Lappalainen, Patricia Bassereau

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

Filopodia are actin-rich membrane protrusions essential for cell morphogenesis, motility, and cancer invasion. How cells control filopodium initiation on the plasma membrane remains elusive. We performed experiments in cellulo, in vitro, and in silico to unravel the mechanism of filopodium initiation driven by the membrane curvature sensor IRSp53 (insulin receptor substrate protein of 53 kDa). We showed that full-length IRSp53 self-assembles into clusters on membranes depending on PIP2. Using well-controlled in vitro reconstitution systems, we demonstrated that IRSp53 clusters recruit the actin polymerase VASP (vasodilator-stimulated phosphoprotein) to assemble actin filaments locally on membranes, leading to the generation of actin-filled membrane protrusions reminiscent of filopodia. By pulling membrane nanotubes from live cells, we observed that IRSp53 can only be enriched and trigger actin assembly in nanotubes at highly dynamic membrane regions. Our work supports a regulation mechanism of IRSp53 in its attributes of curvature sensation and partner recruitment to ensure a precise spatial-temporal control of filopodium initiation.

Original languageEnglish
Pages (from-to)eabp8677
JournalScience Advances
Volume8
Issue number41
DOIs
Publication statusPublished - Oct 14 2022

ASJC Scopus subject areas

  • General

Fingerprint

Dive into the research topics of 'Activated I-BAR IRSp53 clustering controls the formation of VASP-actin-based membrane protrusions'. Together they form a unique fingerprint.

Cite this