A laminin-2, dystroglycan, utrophin axis is required for compartmentalization and elongation of myelin segments

Felipe A. Court, Jane E. Hewitt, Kay Davies, Bruce L. Patton, Antonino Uncini, Lawrence Wrabetz, M. Laura Feltri

Research output: Contribution to journalArticle

45 Scopus citations

Abstract

Animal and plant cells compartmentalize to perform morphogenetic functions. Compartmentalization of myelin-forming Schwann cells may favor elongation of myelin segments to the size required for efficient conduction of nerve impulses. Compartments in myelinated fibers were described by Ramón y Cajal and depend on periaxin, mutated in the hereditary neuropathy Charcot-Marie-Tooth disease type 4F (Charcot-Marie-Tooth 4F). Lack of periaxin in mice causes loss of compartments, formation of short myelin segments (inter-nodes) and reduced nerve conduction velocity. How compartments are formed and maintained, and their relevance to human neuropathies is largely unknown. Here we show that formation of compartments around myelin is driven by the actin cytoskeleton, and maintained by actin and tubulin fences through linkage to the dystroglycan complex. Compartmentalization and establishment of correct internodal length requires the presence of glycosylated dystroglycan, utrophin and extracellular laminin-2/211. A neuropathic patient with reduced internodal length and nerve conduction velocity because of absence of laminin-2/211 (congenital muscular dystrophy 1A) also shows abnormal compartmentalization. These data link formation of compartments through a laminin2, dystroglycan, utrophin, actin axis to internodal length, and provide a common pathogenetic mechanism for two inherited human neuropathies. Other cell types may exploit dystroglycan complexes in similar fashions to create barriers and compartments.

Original languageEnglish (US)
Pages (from-to)3908-3919
Number of pages12
JournalJournal of Neuroscience
Volume29
Issue number12
DOIs
StatePublished - Mar 25 2009

ASJC Scopus subject areas

  • Neuroscience(all)

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    Court, F. A., Hewitt, J. E., Davies, K., Patton, B. L., Uncini, A., Wrabetz, L., & Feltri, M. L. (2009). A laminin-2, dystroglycan, utrophin axis is required for compartmentalization and elongation of myelin segments. Journal of Neuroscience, 29(12), 3908-3919. https://doi.org/10.1523/JNEUROSCI.5672-08.2009