APC2 controls dendrite development by promoting microtubule dynamics

Nat Commun. 2018 Jul 17;9(1):2773. doi: 10.1038/s41467-018-05124-5.

Abstract

Mixed polarity microtubule organization is the signature characteristic of vertebrate dendrites. Oppositely oriented microtubules form the basis for selective cargo trafficking in neurons, however the mechanisms that establish and maintain this organization are unclear. Here, we show that APC2, the brain-specific homolog of tumor-suppressor protein adenomatous polyposis coli (APC), promotes dynamics of minus-end-out microtubules in dendrites. We found that APC2 localizes as distinct clusters along microtubule bundles in dendrites and that this localization is driven by LC8-binding and two separate microtubule-interacting domains. Depletion of APC2 reduces the plus end dynamics of minus-end-out oriented microtubules, increases microtubule sliding, and causes defects in dendritic morphology. We propose a model in which APC2 regulates dendrite development by promoting dynamics of minus-end-out microtubules.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • COS Cells
  • Chlorocebus aethiops
  • Cytoplasmic Dyneins / genetics*
  • Cytoplasmic Dyneins / metabolism
  • Cytoskeletal Proteins / genetics*
  • Cytoskeletal Proteins / metabolism
  • Dendrites / metabolism*
  • Dendrites / ultrastructure
  • Embryo, Mammalian
  • Gene Expression Regulation
  • Genes, Reporter
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • HEK293 Cells
  • Hippocampus / cytology
  • Hippocampus / metabolism*
  • Humans
  • Luminescent Proteins / genetics
  • Luminescent Proteins / metabolism
  • Microtubules / metabolism*
  • Microtubules / ultrastructure
  • Molecular Imaging
  • Neurogenesis / genetics
  • Neurons / metabolism
  • Neurons / ultrastructure
  • Primary Cell Culture
  • Protein Binding
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • Rats
  • Rats, Wistar
  • Signal Transduction
  • Time-Lapse Imaging

Substances

  • APC2 protein, human
  • Cytoskeletal Proteins
  • Luminescent Proteins
  • Protein Isoforms
  • red fluorescent protein
  • Green Fluorescent Proteins
  • DYNLL1 protein, human
  • Cytoplasmic Dyneins