Access

You are not currently logged in.

Access your personal account or get JSTOR access through your library or other institution:

login

Log in to your personal account or through your institution.

Selective Internalization of Sodium Channels in Rat Dorsal Root Ganglion Neurons Infected with Herpes Simplex Virus-1

Nina Storey, David Latchman and Stuart Bevan
The Journal of Cell Biology
Vol. 158, No. 7 (Sep. 30, 2002), pp. 1251-1262
Stable URL: http://www.jstor.org/stable/1621187
Page Count: 12
  • More info
  • Cite this Item
Selective Internalization of Sodium Channels in Rat Dorsal Root Ganglion Neurons Infected with Herpes Simplex Virus-1
Preview not available

Abstract

The neurotropic virus, herpes simplex type 1 (HSV-1), inhibits the excitability of peripheral mammalian neurons, but the molecular mechanism of this effect has not been identified. Here, we use voltage-clamp measurement of ionic currents and an antibody against sodium channels to show that loss of excitability results from the selective, precipitous, and complete internalization of voltage-activated sodium channel proteins from the plasma membrane of neurons dissociated from rat dorsal root ganglion. The internalization process requires viral protein synthesis but not viral encapsulation, and does not alter the density of voltage-activated calcium or potassium channels. However, internalization is blocked completely when viruses lack the neurovirulence factor, infected cell protein 34.5, or when endocytosis is inhibited with bafilomycin A1 or chloroquine. Although it has been recognized for many years that viruses cause cell pathology by interfering with signal transduction pathways, this is the first example of viral pathology resulting from selective internalization of an integral membrane protein. In studying the HSV-induced redistribution of sodium channels, we have uncovered a previously unknown pathway for the rapid and dynamic control of excitability in sensory neurons by internalization of sodium channels.

Page Thumbnails

  • Thumbnail: Page 
1251
    1251
  • Thumbnail: Page 
1252
    1252
  • Thumbnail: Page 
1253
    1253
  • Thumbnail: Page 
1254
    1254
  • Thumbnail: Page 
1255
    1255
  • Thumbnail: Page 
1256
    1256
  • Thumbnail: Page 
1257
    1257
  • Thumbnail: Page 
1258
    1258
  • Thumbnail: Page 
1259
    1259
  • Thumbnail: Page 
1260
    1260
  • Thumbnail: Page 
1261
    1261
  • Thumbnail: Page 
1262
    1262