Accelerated actin filament polymerization from microtubule plus ends

Science. 2016 May 20;352(6288):1004-9. doi: 10.1126/science.aaf1709.

Abstract

Microtubules (MTs) govern actin network remodeling in a wide range of biological processes, yet the mechanisms underlying this cytoskeletal cross-talk have remained obscure. We used single-molecule fluorescence microscopy to show that the MT plus-end-associated protein CLIP-170 binds tightly to formins to accelerate actin filament elongation. Furthermore, we observed mDia1 dimers and CLIP-170 dimers cotracking growing filament ends for several minutes. CLIP-170-mDia1 complexes promoted actin polymerization ~18 times faster than free-barbed-end growth while simultaneously enhancing protection from capping proteins. We used a MT-actin dynamics co-reconstitution system to observe CLIP-170-mDia1 complexes being recruited to growing MT ends by EB1. The complexes triggered rapid growth of actin filaments that remained attached to the MT surface. These activities of CLIP-170 were required in primary neurons for normal dendritic morphology. Thus, our results reveal a cellular mechanism whereby growing MT plus ends direct rapid actin assembly.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Actin Cytoskeleton / chemistry*
  • Actin Cytoskeleton / metabolism
  • Adaptor Proteins, Signal Transducing / chemistry
  • Adaptor Proteins, Signal Transducing / metabolism
  • Animals
  • Cells, Cultured
  • Cytoskeleton / chemistry*
  • Fetal Proteins / chemistry
  • Fetal Proteins / metabolism
  • Formins
  • Humans
  • Microfilament Proteins / chemistry
  • Microfilament Proteins / metabolism
  • Microscopy, Fluorescence
  • Microtubule-Associated Proteins / chemistry*
  • Microtubule-Associated Proteins / genetics
  • Microtubule-Associated Proteins / metabolism
  • Microtubules / chemistry*
  • Microtubules / metabolism
  • Neoplasm Proteins / chemistry*
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism
  • Neurons / metabolism*
  • Nuclear Proteins / chemistry
  • Nuclear Proteins / metabolism
  • Polymerization
  • Protein Isoforms / chemistry
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • Protein Multimerization
  • Rats

Substances

  • Adaptor Proteins, Signal Transducing
  • DIAPH1 protein, human
  • Fetal Proteins
  • Formins
  • Microfilament Proteins
  • Microtubule-Associated Proteins
  • Neoplasm Proteins
  • Nuclear Proteins
  • Protein Isoforms
  • cytoplasmic linker protein 170