Spatial mapping of juxtacrine axo-glial interactions identifies novel molecules in peripheral myelination

Y. Poitelon, S. Bogni, V. Matafora, G. Della-Flora Nunes, E. Hurley, M. Ghidinelli, B. S. Katzenellenbogen, C. Taveggia, N. Silvestri, A. Bachi, A. Sannino, L. Wrabetz and M. L. Feltri ()
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Y. Poitelon: Hunter James Kelly Research Institute, University at Buffalo
S. Bogni: San Raffaele Hospital
V. Matafora: San Raffaele Hospital
G. Della-Flora Nunes: Hunter James Kelly Research Institute, University at Buffalo
E. Hurley: Hunter James Kelly Research Institute, University at Buffalo
M. Ghidinelli: Hunter James Kelly Research Institute, University at Buffalo
B. S. Katzenellenbogen: University of Illinois and College of Medicine
C. Taveggia: San Raffaele Hospital
N. Silvestri: School of Medicine and Biomedical Sciences, University at Buffalo
A. Bachi: San Raffaele Hospital
A. Sannino: University of Salento
L. Wrabetz: Hunter James Kelly Research Institute, University at Buffalo
M. L. Feltri: Hunter James Kelly Research Institute, University at Buffalo

Nature Communications, 2015, vol. 6, issue 1, 1-13

Abstract: Abstract Cell–cell interactions promote juxtacrine signals in specific subcellular domains, which are difficult to capture in the complexity of the nervous system. For example, contact between axons and Schwann cells triggers signals required for radial sorting and myelination. Failure in this interaction causes dysmyelination and axonal degeneration. Despite its importance, few molecules at the axo-glial surface are known. To identify novel molecules in axo-glial interactions, we modified the ‘pseudopodia’ sub-fractionation system and isolated the projections that glia extend when they receive juxtacrine signals from axons. By proteomics we identified the signalling networks present at the glial-leading edge, and novel proteins, including members of the Prohibitin family. Glial-specific deletion of Prohibitin-2 in mice impairs axo-glial interactions and myelination. We thus validate a novel method to model morphogenesis and juxtacrine signalling, provide insights into the molecular organization of the axo-glial contact, and identify a novel class of molecules in myelination.

Date: 2015
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DOI: 10.1038/ncomms9303

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