WDR47 protects neuronal microtubule minus ends from katanin-mediated severing
Buijs, Robin R.; Hummel, Jessica J.A.; Burute, Mithila; Pan, Xingxiu; Cao, Yujie; Stucchi, Riccardo; Altelaar, Maarten; Akhmanova, Anna; Kapitein, Lukas C.; Hoogenraad, Casper C.
(2021) Cell Reports, volume 36, issue 2, pp. 1 - e7
(Article)
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
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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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Keywords: axon, CAMSAP, centrosome, cytoskeleton, dendrite, katanin, microtubule, neuron, WDR47, General Biochemistry,Genetics and Molecular Biology
ISSN: 2211-1247
Publisher: Elsevier Saunders
Note: Funding Information: We thank Prof. K. Jiang (Wuhan University, China) and Dr. G. Far?as (Utrecht University, the Netherlands) for sharing DNA constructs. This work was supported by the Netherlands Organization for Scientific Research (NWO-ALW-VICI to C.C.H. and NWO Graduate Program to R.R.B. [022.003.003]), the Netherlands Organization for Health Research and Development (ZonMW-TOP to C.C.H.) and the European Research Council (ERC) (ERC-consolidator to C.C.H.). R.R.B. designed and performed experiments, analyzed data, and wrote the manuscript. J.J.A.H. cloned constructs, performed pull-down experiments, and edited the manuscript. M.B. performed COS-7 experiments, analyzed data, and edited the manuscript. X.P. and Y.C. generated CRISPR KI constructs and performed experiments. R.S. performed the mass spectrometry experiment. M.A. supervised the mass spectrometry experiment. A.A. gave advice. L.C.K. supervised the COS-7 experiments. C.C.H. designed and supervised the research and wrote and edited the manuscript. C.C.H. is an employee of Genentech, Inc. a member of the Roche group. Funding Information: We thank Prof. K. Jiang (Wuhan University, China) and Dr. G. Farías (Utrecht University, the Netherlands) for sharing DNA constructs. This work was supported by the Netherlands Organization for Scientific Research ( NWO-ALW-VICI to C.C.H. and NWO Graduate Program to R.R.B. [022.003.003]), the Netherlands Organization for Health Research and Development ( ZonMW-TOP to C.C.H.) and the European Research Council (ERC) ( ERC-consolidator to C.C.H.). Publisher Copyright: © 2021 The Author(s)
(Peer reviewed)
