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

[junctional epidermolysis bullosa]

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 .