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.
Highlights
Stomatin-like protein-3 (STOML3) is a member of a large protein family characterized by the presence of a stomatin signature domain [1,2]
A complex of stomatin-family proteins and acid-sensing ion channel (ASIC) family members participate in sensory transduction in invertebrates and vertebrates
We demonstrate that stomatin-like protein-3 (STOML3) interacts with stomatin and acid-sensing ( proton-gated) ion channel (ASIC) subunits and that this occurs in a highly mobile vesicle pool in dorsal root ganglia (DRG) neurons and Chinese hamster ovary cells
Summary
Stomatin-like protein-3 (STOML3) is a member of a large protein family characterized by the presence of a stomatin signature domain [1,2]. PH1511 is a prokaryotic protein, the amino acid sequence of the stomatin domain is remarkably close to that of its mammalian orthologues. MEC-2, a Caenorhabditis elegans stomatin-like protein, is required for mechanosensitivity and is necessary for the function of MEC-4/MEC-10-containing mechanosensitive channels in the nematode worm [10,12,16 –18]. Mammalian orthologues of MEC-4 and MEC-10, the acidsensing ( proton-gated) ion channels ASIC2a/b and ASIC3, have been implicated in mechanosensation [19,20,21,22]: The ASICs can functionally interact with stomatin and STOML3, and such interactions may contribute to the modulation of sensory neuron mechanosensitivity seen after deletion of ASIC genes [9,23]. Evidence from targeted deletion of the STOML3 gene strongly suggests that this protein is an essential regulator of native mechanosensitive ion channels [2,9]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
