Cytolinker Gas2L1 regulates axon morphology through microtubule-modulated actin stabilization

Dieudonnée van de Willige, Jessica Ja Hummel, Celine Alkemade, Olga I Kahn, Franco Kc Au, Robert Z Qi, Marileen Dogterom, Gijsje H Koenderink*, Casper C Hoogenraad*, Anna Akhmanova*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

16 Citations (Web of Science)

Abstract

Crosstalk between the actin and microtubule cytoskeletons underlies cellular morphogenesis. Interactions between actin filaments and microtubules are particularly important for establishing the complex polarized morphology of neurons. Here, we characterized the neuronal function of growth arrest-specific 2-like 1 (Gas2L1), a protein that can directly bind to actin, microtubules and microtubule plus-end-tracking end binding proteins. We found that Gas2L1 promotes axon branching, but restricts axon elongation in cultured rat hippocampal neurons. Using pull-down experiments and in vitro reconstitution assays, in which purified Gas2L1 was combined with actin and dynamic microtubules, we demonstrated that Gas2L1 is autoinhibited. This autoinhibition is relieved by simultaneous binding to actin filaments and microtubules. In neurons, Gas2L1 primarily localizes to the actin cytoskeleton and functions as an actin stabilizer. The microtubule-binding tail region of Gas2L1 directs its actin-stabilizing activity towards the axon. We propose that Gas2L1 acts as an actin regulator, the function of which is spatially modulated by microtubules.

Original languageEnglish
Article numbere47732
Number of pages20
JournalEmbo Reports
Volume20
Issue number11
DOIs
Publication statusPublished - 5 Nov 2019
Externally publishedYes

Keywords

  • Actins/metabolism
  • Animals
  • Axons/metabolism
  • Biomarkers
  • COS Cells
  • Chlorocebus aethiops
  • Female
  • HEK293 Cells
  • Hippocampus/metabolism
  • Humans
  • Male
  • Microfilament Proteins/metabolism
  • Microtubules/metabolism
  • Molecular Imaging
  • Neurites/metabolism
  • Neurons/cytology
  • Protein Binding
  • Protein Stability
  • Protein Transport
  • Pyramidal Cells/cytology
  • Rats
  • neuronal development
  • in vitro reconstitution
  • DRIVEN
  • DROSOPHILA SHORT STOP
  • NEURITE OUTGROWTH
  • GROWTH
  • IN-VITRO RECONSTITUTION
  • SPECTRAPLAKINS
  • cytoskeleton
  • DYNAMIC MICROTUBULES
  • NEURONS
  • cytolinker
  • TIP
  • axon
  • PROTEINS

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