Cell adhesion molecule L1 contributes to neuronal excitability regulating the function of voltage-gated Na+ channels

J Cell Sci. 2016 May 1;129(9):1878-91. doi: 10.1242/jcs.182089. Epub 2016 Mar 16.


L1 (also known as L1CAM) is a trans-membrane glycoprotein mediating neuron-neuron adhesion through homophilic and heterophilic interactions. Although experimental evidence has implicated L1 in axonal outgrowth, fasciculation and pathfinding, its contribution to voltage-gated Na(+) channel function and membrane excitability has remained unknown. Here, we show that firing rate, single cell spiking frequency and Na(+) current density are all reduced in hippocampal excitatory neurons from L1-deficient mice both in culture and in slices owing to an overall reduced membrane expression of Na(+) channels. Remarkably, normal firing activity was restored when L1 was reintroduced into L1-deficient excitatory neurons, indicating that abnormal firing patterns are not related to developmental abnormalities, but are a direct consequence of L1 deletion. Moreover, L1 deficiency leads to impairment of action potential initiation, most likely due to the loss of the interaction of L1 with ankyrin G that produces the delocalization of Na(+) channels at the axonal initial segment. We conclude that L1 contributes to functional expression and localization of Na(+) channels to the neuronal plasma membrane, ensuring correct initiation of action potential and normal firing activity.

Keywords: Action potential; Adhesion molecule; CRASH syndrome; Firing activity; L1CAM; Sodium channels.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Membrane / genetics
  • Cell Membrane / metabolism*
  • Gene Expression Regulation / physiology*
  • Hippocampus / cytology
  • Hippocampus / metabolism*
  • Mice
  • Mice, Knockout
  • Neural Cell Adhesion Molecule L1 / genetics
  • Neural Cell Adhesion Molecule L1 / metabolism*
  • Neurons / cytology
  • Neurons / metabolism*
  • Voltage-Gated Sodium Channels / biosynthesis*
  • Voltage-Gated Sodium Channels / genetics


  • Neural Cell Adhesion Molecule L1
  • Voltage-Gated Sodium Channels