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Spastin Interacts with CRMP 5 to Promote Neurite Outgrowth by Controlling the Microtubule Dynamics
Author(s) -
Ji Zhisheng,
Zhang Guowei,
Chen Li,
Li Jiong,
Yang Yuhao,
Cha Caihui,
Zhang Jifeng,
Lin Hongsheng,
Guo Guoqing
Publication year - 2018
Publication title -
developmental neurobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.716
H-Index - 129
eISSN - 1932-846X
pISSN - 1932-8451
DOI - 10.1002/dneu.22640
Subject(s) - neurite , microtubule , microbiology and biotechnology , growth cone , microtubule polymerization , biology , microtubule associated protein , microtubule nucleation , chemistry , axon , tubulin , in vitro , biochemistry , cell , centrosome , cell cycle
ABSTRACT 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 ( CRMP 5) provides structural support and serves as a track for cargo transport by promoting microtubule polymerization. Nevertheless, how spastin and CRMP 5 cooperate to regulate neurite outgrowth by controlling the microtubule dynamics needs to be elucidated. In our present study, spastin interacted with CRMP 5 in vitro and in vivo . The binding domains for the spastin and CRMP 5 interaction were the N‐terminal fragment of spastin (residues 270–328) and the C‐terminal fragment of CRMP 5 (residues 472–564). Spastin and its truncation mutants, including the microtubule‐binding domain ( MTBD ) and ATP ases associated with diverse cellular activities ( AAA ) domain, were necessary for the severing of microtubules. Furthermore, we demonstrated that microtubule polymerization of CRMP 5 interfered with the microtubule‐severing function of spastin. Knocking down either spastin or CRMP 5 inhibited neurite outgrowth in hippocampal neurons. However, co‐transfected spastin and CRMP 5 promoted the outgrowth of neurites including dendrites and axons. Taken together, our data support a model in which the spastin interaction with CRMP 5 promotes neurite outgrowth by controlling the microtubule dynamics.