APC2 controls dendrite development by promoting microtubule dynamics

Olga I Kahn; Philipp Schätzle; Dieudonnée van de Willige; Roderick P Tas; Feline W Lindhout; Sybren Portegies; Lukas C Kapitein; Casper C Hoogenraad

doi:10.1038/s41467-018-05124-5

APC2 controls dendrite development by promoting microtubule dynamics

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

Authors

Olga I Kahn¹, Philipp Schätzle¹, Dieudonnée van de Willige¹, Roderick P Tas¹, Feline W Lindhout¹, Sybren Portegies¹, Lukas C Kapitein¹, Casper C Hoogenraad²

Affiliations

¹ Cell Biology, Department of Biology, Faculty of Science, Utrecht University, 3584 CH, Utrecht, The Netherlands.
² Cell Biology, Department of Biology, Faculty of Science, Utrecht University, 3584 CH, Utrecht, The Netherlands. [email protected].

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
Red Fluorescent Protein
Signal Transduction
Time-Lapse Imaging

Substances

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