Annexin II light chain regulates sensory neuron-specific sodium channel expression.
The tetrodotoxin-resistant sodium channel Na(V)1.8/SNS is expressed exclusively in sensory neurons and appears to have an important role in pain pathways. Unlike other sodium channels, Na(V)1.8 is poorly expressed in cell lines even in the presence of accessory beta-subunits. Here we identify annexin II light chain (p11) as a regulatory factor that facilitates the expression of Na(V)1.8. p11 binds directly to the amino terminus of Na(V)1.8 and promotes the translocation of Na(V)1.8 to the plasma membrane, producing functional channels. The endogenous Na(V)1.8 current in sensory neurons is inhibited by antisense downregulation of p11 expression. Because direct association with p11 is required for functional expression of Na(V)1.8, disrupting this interaction may be a useful new approach to downregulating Na(V)1.8 and effecting analgesia.
Okuse
Kenji
K
Department of Biology, University College London, Gower Street, London WC1E 6BT, UK.
Malik-Hall
Misbah
M
Baker
Mark D
MD
Poon
W-Y Louisa
WY
Kong
Haeyoung
H
Chao
Moses V
MV
Wood
John N
JN
D000818:Animals; D017306:Annexin A2 / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D016466:CHO Cells; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D006224:Cricetinae; D005455:Fluorescent Antibody Technique; D005727:Ganglia, Spinal / Q000166:cytology; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D017403:In Situ Hybridization; D008970:Molecular Weight; D062559:NAV1.8 Voltage-Gated Sodium Channel; D020932:Nerve Growth Factor / Q000494:pharmacology; D009475:Neurons, Afferent / Q000187:drug effects / Q000378:metabolism*; D009479:Neuropeptides / Q000235:genetics* / Q000378:metabolism*; D009928:Organ Specificity; D018408:Patch-Clamp Techniques; D011485:Protein Binding; D021122:Protein Subunits; D021381:Protein Transport; D016372:RNA, Antisense / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D015222:Sodium Channels / Q000235:genetics* / Q000378:metabolism*; D020798:Two-Hybrid System Techniques
D017306:Annexin A2; D062559:NAV1.8 Voltage-Gated Sodium Channel; D009479:Neuropeptides; D021122:Protein Subunits; D016372:RNA, Antisense; D012333:RNA, Messenger; C568319:Scn10a protein, rat; D015222:Sodium Channels; D020932:Nerve Growth Factor