Process outgrowth in oligodendrocytes is mediated by CNP, a novel microtubule assembly myelin protein

• Published in: The Journal of cell biology Vol. 170; no. 4; pp. 661 - 673
• Main Authors: Lee, John, Gravel, Michel, Zhang, Rulin, Thibault, Pierre, Braun, Peter E
• Format: Journal Article
• Language: English
• Published: United States Rockefeller University Press 15.08.2005; The Rockefeller University Press
• Subjects: 2',3'-Cyclic-Nucleotide Phosphodiesterases - chemistry; 2',3'-Cyclic-Nucleotide Phosphodiesterases - metabolism; Actins; Actins - metabolism; Amino Acid Sequence; Animals; Cell Surface Extensions - enzymology; Cells, Cultured; Cercopithecus aethiops; COS Cells; Cytoskeleton; Cytoskeleton - enzymology; Dimerization; Glycine - metabolism; Lysine - metabolism; Mice; Microtubules; Microtubules - enzymology; Molecular Sequence Data; Mutation; Myelin; Myelin Proteins - chemistry; Myelin Proteins - metabolism; Neurons; Neuroscience; Oligodendroglia; Oligodendroglia - cytology; Oligodendroglia - enzymology; Polymerization; Protein Binding; Protein Structure, Tertiary; Protein Transport; Proteins; Pseudopodia; Rats; Tubulin - metabolism
• ISSN: 0021-9525; 1540-8140
• DOI: 10.1083/jcb.200411047

Oligodendrocytes (OLs) extend arborized processes that are supported by microtubules (MTs) and microfilaments. Little is known about proteins that modulate and interact with the cytoskeleton during myelination. Several lines of evidence suggest a role for 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNP) in mediating process formation in OLs. In this study, we report that tubulin is a major CNP-interacting protein. In vitro, CNP binds preferentially to tubulin heterodimers compared with MTs and induces MT assembly by copolymerizing with tubulin. CNP overexpression induces dramatic morphology changes in both glial and nonglial cells, resulting in MT and F-actin reorganization and formation of branched processes. These morphological effects are attributed to CNP MT assembly activity; branched process formation is either substantially reduced or abolished with the expression of loss-of-function mutants. Accordingly, cultured OLs from CNP-deficient mice extend smaller outgrowths with less arborized processes. We propose that CNP is an important component of the cytoskeletal machinery that directs process outgrowth in OLs.