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Published 15 August 2005. doi:10.1083/jcb.200411047
The Rockefeller University Press, 0021-9525 $8.00
JCB, Volume 170, Number 4, 661-673
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Article

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



John Lee1, Michel Gravel1, Rulin Zhang2, Pierre Thibault3, and Peter E. Braun1

1 Department of Biochemistry, McGill University, Montreal, Quebec H3G 1Y6, Canada
2 WEMB Biochem, Inc., Toronto, Ontario M9W 1E7, Canada
3 Institut de Recherches en Immunologie et Cancer, Université de Montréal, Montreal, Quebec H3C 3J7, Canada

Correspondence to John Lee: johnlee{at}gene.com

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.

Abbreviations used in this paper: CF, catalytic fragment; CMV, cytomegalo virus; CNP, 2',3'-cyclic nucleotide 3'-phosphodiesterase; MAP, MT-associated protein; MT, microtubule; MTOC, MT-organizing center; OL, oligodendrocyte; RSV, rous sarcoma virus.


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