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Laminin-332 coordinates mechanotransduction and growth cone bifurcation in sensory neurons

Item Type:Article
Title:Laminin-332 coordinates mechanotransduction and growth cone bifurcation in sensory neurons
Creators Name:Chiang, L.Y. and Poole, K. and Oliveira, B.E. and Duarte, N. and Bernal Sierra, Y.A. and Bruckner-Tuderman, L. and Koch, M. and Hu, J. and Lewin, G.R.
Abstract:Laminin-332 is a major component of the dermo-epidermal skin basement membrane and maintains skin integrity. The transduction of mechanical force into electrical signals by sensory endings in the skin requires mechanosensitive channels. We found that mouse epidermal keratinocytes produce a matrix that is inhibitory for sensory mechanotransduction and that the active molecular component is laminin-332. Substrate-bound laminin-332 specifically suppressed one type of mechanosensitive current (rapidly adapting) independently of integrin-receptor activation. This mechanotransduction suppression could be exerted locally and was mediated by preventing the formation of protein tethers necessary for current activation. We also found that laminin-332 could locally control sensory axon branching behavior. Loss of laminin-332 in humans led to increased sensory terminal branching and may lead to a de-repression of mechanosensitive currents. These previously unknown functions for this matrix molecule may explain some of the extreme pain experienced by individuals with epidermolysis bullosa who are deficient in laminin-332.
Keywords:Atomic Force Microscopy, Axons, Cell Adhesion Molecules, Cellular Mechanotransduction, Coculture Techniques, Collagen Type VII, Cultured Cells, Growth Cones, Junctional Epidermolysis Bullosa, Keratinocytes, Lidocaine, Membrane Potentials, Neurofilament Proteins, Newborn Animals, Patch-Clamp Techniques, Physical Stimulation, Physiological Adaptation, Reaction Time, Sensory Receptor Cells, Skin, Sodium Channel Blockers, Spinal Ganglia, TRPV Cation Channels, Tetrodotoxin, Time Factors, Transmission Electron Microscopy, Ubiquitin Thiolesterase, Animals, Mice
Source:Nature Neuroscience
Publisher:Nature Publishing Group
Page Range:993-1000
Date:3 July 2011
Official Publication:https://doi.org/10.1038/nn.2873
PubMed:View item in PubMed

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