WDR47 protects neuronal microtubule minus ends from katanin-mediated severing
Robin R. Buijs,
Jessica J.A. Hummel,
Mithila Burute,
Xingxiu Pan,
Yujie Cao,
Riccardo Stucchi,
Maarten Altelaar,
Anna Akhmanova,
Lukas C. Kapitein,
Casper C. Hoogenraad
Affiliations
Robin R. Buijs
Cell Biology, Neurobiology and Biophysics, Department of Biology, Faculty of Science, Utrecht University, 3584 Utrecht, the Netherlands
Jessica J.A. Hummel
Cell Biology, Neurobiology and Biophysics, Department of Biology, Faculty of Science, Utrecht University, 3584 Utrecht, the Netherlands
Mithila Burute
Cell Biology, Neurobiology and Biophysics, Department of Biology, Faculty of Science, Utrecht University, 3584 Utrecht, the Netherlands
Xingxiu Pan
Cell Biology, Neurobiology and Biophysics, Department of Biology, Faculty of Science, Utrecht University, 3584 Utrecht, the Netherlands
Yujie Cao
Cell Biology, Neurobiology and Biophysics, Department of Biology, Faculty of Science, Utrecht University, 3584 Utrecht, the Netherlands
Riccardo Stucchi
Cell Biology, Neurobiology and Biophysics, Department of Biology, Faculty of Science, Utrecht University, 3584 Utrecht, the Netherlands; Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, Utrecht University, 3584 Utrecht, the Netherlands
Maarten Altelaar
Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, Utrecht University, 3584 Utrecht, the Netherlands
Anna Akhmanova
Cell Biology, Neurobiology and Biophysics, Department of Biology, Faculty of Science, Utrecht University, 3584 Utrecht, the Netherlands
Lukas C. Kapitein
Cell Biology, Neurobiology and Biophysics, Department of Biology, Faculty of Science, Utrecht University, 3584 Utrecht, the Netherlands
Casper C. Hoogenraad
Cell Biology, Neurobiology and Biophysics, Department of Biology, Faculty of Science, Utrecht University, 3584 Utrecht, the Netherlands; Department of Neuroscience, Genentech, Inc., South San Francisco, CA 94080, USA; Corresponding author
Summary: 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.
