A human IgM signals axon outgrowth: Coupling lipid raft to microtubules

Xiaohua Xu, Arthur E. Warrington, Brent R. Wright, Allan J. Bieber, Virginia Van Keulen, Larry R. Pease, Moses Rodriguez

Research output: Contribution to journalArticle

24 Scopus citations

Abstract

Mouse and human IgMs support neurite extension from primary cerebellar granule neurons. In this study using primary hippocampal and cortical neurons, we demonstrate that a recombinant human IgM, rHIgM12, promotes axon outgrowth by coupling membrane domains (lipid rafts) to microtubules. rHIgM12 binds to the surface of neuron and induces clustering of cholesterol and ganglioside GM1. After cell binding and membrane fractionation, rHIgM12 gets segregated into two pools, one associated with lipid raft fractions and the other with the detergent-insoluble cytoskeleton-containing pellet. Membrane-bound rHIgM12 co-localized with microtubules and co-immuno precipitated with β3-tubulin. rHIgM12-membrane interaction also enhanced the tyrosination of α-tubulin indicating a stabilization of new neurites. When presented as a substrate, rHIgM12 induced axon outgrowth from primary neurons. We now demonstrate that a recombinant human mAb can induce signals in neurons that regulate membrane lipids and microtubule dynamics required for axon extension. We propose that the pentameric structure of the IgM is critical to cross-link membrane lipids and proteins resulting in signaling cascades.

Original languageEnglish (US)
Pages (from-to)100-112
Number of pages13
JournalJournal of neurochemistry
Volume119
Issue number1
DOIs
StatePublished - Oct 1 2011

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Keywords

  • IgM
  • axon
  • lipid raft
  • membrane
  • microtubule

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Xu, X., Warrington, A. E., Wright, B. R., Bieber, A. J., Van Keulen, V., Pease, L. R., & Rodriguez, M. (2011). A human IgM signals axon outgrowth: Coupling lipid raft to microtubules. Journal of neurochemistry, 119(1), 100-112. https://doi.org/10.1111/j.1471-4159.2011.07416.x