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

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.

Jmy regulates oligodendrocyte differentiation via modulation of actin cytoskeleton dynamics

“…Data represented as mean 6 SEM of n 5 55 cells per condition, randomly sampled from three independent experiments. (f) Individual trajectories of shCtr-and shJmy-OLs from their point of origin at the start of differentiation (n 5 55 in each group) [Color figure can be viewed at wileyonlinelibrary.com] function and cell-cell interactions (Feltrin et al, 2012;Holt & Schuman, 2013;Mili et al, 2008;Poitelon et al, 2015). Although ours and other published data suggest that the same functional classes of molecules are polarized in specialized cellular compartments, we identified an OPC-specific signature of transcripts enriched in membrane protrusion.…”

A dual role for Integrin α6β4 in modulating hereditary neuropathy with liability to pressure palsies

“…Animals were analyzed at 30 days of age as described previously (Poitelon et al 2015). Briefly, mice were anesthetized with tribromoethanol, 0.02 mL/g of body weight, and placed under a heating lamp to avoid hypothermia.…”

Prohibitin 1 is essential to preserve mitochondria and myelin integrity in Schwann cells.

“…We recently identi ed prohibitin 2 (PHB2) as an essential protein for developmental myelination in mice 7 . Moreover, we found evidence that PHB2 can localize to the axon-SC interface and is important in the early contact between these two cell types 7 .…”

“…We recently identi ed prohibitin 2 (PHB2) as an essential protein for developmental myelination in mice 7 . Moreover, we found evidence that PHB2 can localize to the axon-SC interface and is important in the early contact between these two cell types 7 . Although prohibitins have been reported in diverse subcellular localizations, they are most well known for their role in mitochondria, where they carry out many of their functions 8 .…”