title: Regulation of ASIC channels by a stomatin/STOML3 complex located in a mobile vesicle pool in sensory neurons.
abstract: A complex of stomatin-family proteins and acid-sensing (proton-gated) ion channel (ASIC) family members participate in sensory transduction in invertebrates and vertebrates. Here, we have examined the role of the stomatin-family protein stomatin-like protein-3 (STOML3) in this process. We demonstrate that STOML3 interacts with stomatin and ASIC subunits and that this occurs in a highly mobile vesicle pool in dorsal root ganglia (DRG) neurons and Chinese hamster ovary cells. We identify a hydrophobic region in the N-terminus of STOML3 that is required for vesicular localization of STOML3 and regulates physical and functional interaction with ASICs. We further characterize STOML3-containing vesicles in DRG neurons and show that they are Rab11-positive, but not part of the early-endosomal, lysosomal or Rab14-dependent biosynthetic compartment. Moreover, uncoupling of vesicles from microtubules leads to incorporation of STOML3 into the plasma membrane and increased acid-gated currents. Thus, STOML3 defines a vesicle pool in which it associates with molecules that have critical roles in sensory transduction. We suggest that the molecular features of this vesicular pool may be characteristic of a 'transducosome' in sensory neurons.
authors: Department of Neuroscience, Max-Delbrück Center for Molecular Medicine, Robert-Rössle-Strasse 10, 13092 Berlin-Buch, Germany.
authors: Liudmila
authors: L
authors: Lapatsina
authors: Julia A
authors: JA
authors: Jira
authors: Ewan St J
authors: ES
authors: Smith
authors: Kate
authors: K
authors: Poole
authors: Alexey
authors: A
authors: Kozlenkov
authors: Daniel
authors: D
authors: Bilbao
authors: Gary R
authors: GR
authors: Lewin
authors: Paul A
authors: PA
authors: Heppenstall
mesh_terms: D062565:Acid Sensing Ion Channels / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001798:Blood Proteins / Q000235:genetics / Q000378:metabolism*; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D005727:Ganglia, Spinal / Q000166:cytology / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D011984:Sensory Receptor Cells / Q000166:cytology / Q000378:metabolism*; D022161:Transport Vesicles / Q000235:genetics / Q000378:metabolism*; D020691:rab GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism; D000099193:rab11 GTP-Binding Proteins
chemical_list: D062565:Acid Sensing Ion Channels; D001798:Blood Proteins; D008565:Membrane Proteins; D046912:Multiprotein Complexes; D009419:Nerve Tissue Proteins; D020691:rab GTP-Binding Proteins; D000099193:rab11 GTP-Binding Proteins; C568267:ASIC1 protein, mouse; C488964:Stom protein, mouse; C461699:Stoml3 protein, mouse; C555882:Rab14 protein, mouse