Ndel1 controls the dynein-mediated transport of vimentin during neurite outgrowth.
Ndel1, the mammalian homologue of the Aspergillus nidulans NudE, is emergently viewed as an integrator of the cytoskeleton. By regulating the dynamics of microtubules and assembly of neuronal intermediate filaments (IFs), Ndel1 promotes neurite outgrowth, neuronal migration, and cell integrity (1-6). To further understand the roles of Ndel1 in cytoskeletal dynamics, we performed a tandem affinity purification of Ndel1-interacting proteins. We isolated a novel Ndel1 molecular complex composed of the IF vimentin, the molecular motor dynein, the lissencephaly protein Lis1, and the cis-Golgi-associated protein alphaCOP. Ndel1 promotes the interaction between Lis1, alphaCOP, and the vimentin-dynein complex. The functional result of this complex is activation of dynein-mediated transport of vimentin. A loss of Ndel1 functions by RNA interference fails to incorporate Lis1/alphaCOP in the complex, reduces the transport of vimentin, and culminates in IF accumulations and altered neuritogenesis. Our findings reveal a novel regulatory mechanism of vimentin transport during neurite extension that may have implications in diseases featuring transport/trafficking defects and impaired regeneration.
Shim
Su Yeon
SY
Department of Clinical Neurosciences, Hotchkiss Brain Institute, University of Calgary, Calgary T2N 4N1, Canada.
Samuels
Benjamin Adam
BA
Wang
Jian
J
Neumayer
Gernot
G
Belzil
Camille
C
Ayala
Ramses
R
Shi
Yang
Y
Shi
Yujiang
Y
Tsai
Li-Huei
LH
Nguyen
Minh Dang
MD
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000378:metabolism; D000818:Animals; D002846:Chromatography, Affinity; D004398:Dyneins / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000302:isolation & purification / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism; D008954:Models, Biological; D009419:Nerve Tissue Proteins / Q000378:metabolism; D016501:Neurites / Q000378:metabolism*; D011485:Protein Binding; D021381:Protein Transport; D034622:RNA Interference; D020798:Two-Hybrid System Techniques; D014746:Vimentin / Q000378:metabolism*
D008869:Microtubule-Associated Proteins; C525094:Nde1 protein, human; D009419:Nerve Tissue Proteins; D014746:Vimentin; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; C084102:PAFAH1B1 protein, human; D004398:Dyneins