4.8 Article

WDR47 protects neuronal microtubule minus ends from katanin-mediated severing

Journal

CELL REPORTS
Volume 36, Issue 2, Pages -

Publisher

CELL PRESS
DOI: 10.1016/j.celrep.2021.109371

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Funding

  1. Netherlands Organization for Scientific Research (NWO-ALWVICI )
  2. NWO Graduate Program [022.003.003]
  3. Netherlands Organization for Health Research and Development (ZonMWTOP)
  4. European Research Council (ERC) (ERC-consolidator)

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Experimental evidence shows that the neuron-enriched protein WDR47 interacts with CAMSAPs, playing a critical role in axon and dendrite development. WDR47 accumulates at CAMSAP2-decorated microtubules, maintaining CAMSAP2 stretches and protecting minus ends from katanin-mediated severing.
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.

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