title: Process outgrowth in oligodendrocytes is mediated by CNP, a novel microtubule assembly myelin protein.
abstract: 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.
authors.affiliation: Department of Biochemistry, McGill University, Montreal, Quebec, Canada. johnlee@gene.com
authors.forename: John
authors.initials: J
authors.lastname: Lee
authors.forename: Michel
authors.initials: M
authors.lastname: Gravel
authors.forename: Rulin
authors.initials: R
authors.lastname: Zhang
authors.forename: Pierre
authors.initials: P
authors.lastname: Thibault
authors.forename: Peter E
authors.initials: PE
authors.lastname: Braun
mesh_terms: D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases / Q000737:chemistry / Q000378:metabolism*; D000199:Actins / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D022081:Cell Surface Extensions / Q000201:enzymology*; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D003599:Cytoskeleton / Q000201:enzymology; D019281:Dimerization; D005998:Glycine / Q000378:metabolism; D008239:Lysine / Q000378:metabolism; D051379:Mice; D008870:Microtubules / Q000201:enzymology*; D008969:Molecular Sequence Data; D009185:Myelin Proteins / Q000737:chemistry / Q000378:metabolism*; D009836:Oligodendroglia / Q000166:cytology / Q000201:enzymology*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D051381:Rats; D014404:Tubulin / Q000378:metabolism
chemical_list: D000199:Actins; D009185:Myelin Proteins; D014404:Tubulin; D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases; D008239:Lysine; D005998:Glycine