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

作者：Xu Xiaohua; Warrington Arthur E; Wright Brent R; Bieber Allan J; Van Keulen Virginia; Pease Larry R; Rodriguez Moses^*

来源：Journal of Neurochemistry, 2011, 119(1): 100-112.

DOI：10.1111/j.1471-4159.2011.07416.x

• axon
• IgM
• lipid raft
• membrane
• microtubule

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 beta 3-tubulin. rHIgM12-membrane interaction also enhanced the tyrosination of alpha-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.

• 出版日期2011-10