4.3 Article

Spastin Interacts with CRMP5 to Promote Neurite Outgrowth by Controlling the Microtubule Dynamics

Journal

DEVELOPMENTAL NEUROBIOLOGY
Volume 78, Issue 12, Pages 1191-1205

Publisher

WILEY
DOI: 10.1002/dneu.22640

Keywords

spastin; CRMP5; microtubule dynamics; neurite outgrowth; neuron

Funding

  1. National Natural Science Foundation of China [81571191, 81771144, 81771331]
  2. Natural Science Foundation of Guangdong Province, China [2017B030311002, 2017A030313595]
  3. Guangzhou science and technology project [201605130849016]

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Changing the microtubule dynamics is sufficient to alter the axon and dendrite specification and development. Spastin participates in the growth and regeneration of neurites by severing microtubules into small segments, and collapsin response mediator protein 5 (CRMP5) provides structural support and serves as a track for cargo transport by promoting microtubule polymerization. Nevertheless, how spastin and CRMP5 cooperate to regulate neurite outgrowth by controlling the microtubule dynamics needs to be elucidated. In our present study, spastin interacted with CRMP5 in vitro and in vivo. The binding domains for the spastin and CRMP5 interaction were the N-terminal fragment of spastin (residues 270-328) and the C-terminal fragment of CRMP5 (residues 472-564). Spastin and its truncation mutants, including the microtubule-binding domain (MTBD) and ATPases associated with diverse cellular activities (AAA) domain, were necessary for the severing of microtubules. Furthermore, we demonstrated that microtubule polymerization of CRMP5 interfered with the microtubule-severing function of spastin. Knocking down either spastin or CRMP5 inhibited neurite outgrowth in hippocampal neurons. However, co-transfected spastin and CRMP5 promoted the outgrowth of neurites including dendrites and axons. Taken together, our data support a model in which the spastin interaction with CRMP5 promotes neurite outgrowth by controlling the microtubule dynamics. (c) 2018 Wiley Periodicals, Inc.

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