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The Journal of Neuroscience, April 2, 2008, 28(14):3604-3614; doi:10.1523/JNEUROSCI.5278-07.2008

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Cellular/Molecular
Protein 600 Is a Microtubule/Endoplasmic Reticulum-Associated Protein in CNS Neurons

Su Yeon Shim,¹ Jian Wang,¹ Naoyuki Asada,³ Gernot Neumayer,¹ Hong Chi Tran,¹ Kei-ichiro Ishiguro,² Kamon Sanada,³ Yoshihiro Nakatani,² and Minh Dang Nguyen¹

¹Hotchkiss Brain Institute, Departments of Clinical Neurosciences, Cell Biology and Anatomy, and Biochemistry and Molecular Biology, University of Calgary, Calgary, Alberta, Canada T2N 4N1, ²Dana Farber Cancer Institute, Boston, Massachusetts 02115, and ³Precursory Research for Embryonic Science and Technology, Japan Science and Technology Agency, and Department of Developmental Neuroscience, Osaka University, Graduate School of Medicine, Osaka 565-0871, Japan

Correspondence should be addressed to Dr. Minh Dang Nguyen, Hotchkiss Brain Institute, University of Calgary, Departments of Clinical Neurosciences, Cell Biology and Anatomy, Biochemistry and Molecular Biology, 3330 Hospital Drive Northwest, Heritage Medical Research Building, Room 151, Calgary, Alberta, Canada T2N 4N1. Email: mdnguyen{at}ucalgary.ca

There is an increasing body of literature pointing to cytoskeletal proteins as spatial organizers and interactors of organelles. In this study, we identified protein 600 (p600) as a novel microtubule-associated protein (MAP) developmentally regulated in neurons. p600 exhibits the unique feature to interact with the endoplasmic reticulum (ER). Silencing of p600 by RNA interference (RNAi) destabilizes neuronal processes in young primary neurons undergoing neurite extension and containing scarce staining of the ER marker Bip. Furthermore, in utero electroporation of p600 RNAi alters neuronal migration, a process that depends on synergistic actions of microtubule dynamics and ER functions. p600-depleted migrating neurons display thin, crooked, and "zigzag" leading process with very few ER membranes. Thus, p600 constitutes the only known MAP to associate with the ER in neurons, and this interaction may impact on multiple cellular processes ranging from neuronal development to neuronal maturation and plasticity.

Key words: cytoarchitecture; cytoskeleton; development; differentiation; migration; neurite

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Received Nov. 28, 2007; revised March 1, 2008; accepted March 1, 2008.

Correspondence should be addressed to Dr. Minh Dang Nguyen, Hotchkiss Brain Institute, University of Calgary, Departments of Clinical Neurosciences, Cell Biology and Anatomy, Biochemistry and Molecular Biology, 3330 Hospital Drive Northwest, Heritage Medical Research Building, Room 151, Calgary, Alberta, Canada T2N 4N1. Email: mdnguyen{at}ucalgary.ca

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