WDR47 protects neuronal microtubule minus ends from katanin-mediated severing

Cell Rep. 2021 Jul 13;36(2):109371. doi: 10.1016/j.celrep.2021.109371.

Abstract

Axons and dendrites are long extensions of neurons that contain arrays of noncentrosomal microtubules. Calmodulin-regulated spectrin-associated proteins (CAMSAPs) bind to and stabilize free microtubule minus ends and are critical for proper neuronal development and function. Previous studies have shown that the microtubule-severing ATPase katanin interacts with CAMSAPs and limits the length of CAMSAP-decorated microtubule stretches. However, how CAMSAP and microtubule minus end dynamics are regulated in neurons is poorly understood. Here, we show that the neuron-enriched protein WDR47 interacts with CAMSAPs and is critical for axon and dendrite development. We find that WDR47 accumulates at CAMSAP2-decorated microtubules, is essential for maintaining CAMSAP2 stretches, and protects minus ends from katanin-mediated severing. We propose a model where WDR47 protects CAMSAP2 at microtubule minus ends from katanin activity to ensure proper stabilization of the neuronal microtubule network.

Keywords: CAMSAP; WDR47; axon; centrosome; cytoskeleton; dendrite; katanin; microtubule; neuron.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Axons / metabolism
  • COS Cells
  • Chlorocebus aethiops
  • Dendrites / metabolism
  • Female
  • Gene Knockdown Techniques
  • HEK293 Cells
  • Humans
  • Katanin* / metabolism
  • Microtubule-Associated Proteins* / metabolism
  • Microtubules* / metabolism
  • Neurons* / metabolism
  • Neuroprotection*
  • Protein Binding
  • Rats
  • Rats, Wistar

Substances

  • Katanin
  • Microtubule-Associated Proteins
  • WDR47 protein, rat