The Molecular Basis of Touch Sensation As Modeled in Caenorhabditis elegans

Laura Bianchi, Monica Driscoll

Research output: Chapter in Book/Report/Conference proceedingChapter

3 Citations (Scopus)

Abstract

One of the looming mysteries in signal transduction today is the question of how mechanical signals, such as pressure or stretch, are sensed. Elegant electrophysiological studies in organisms ranging from bacteria to mammals support that mechanotransduction can be mediated by ion channels that gate in response to mechanical stimuli. Despite the importance of the molecular identification of these ion channels for elaborating mechanisms of mechanotransduction, genes encoding mechanosensitive ion channels eluded cloning efforts for a long time. Breakthroughs in the understanding of mechanosensitive channels have come from genetic analyses of touch sensation in Caenorhabditis elegans and Drosophila. In C. elegans, screens for touch-insensitive mutants identified two genes, mec-4 and mec-10, that encode channel subunits implicated in touch sensation and are postulated to be the core of a mechanotransducing ion channel complex. mec-4 and mec-10 encode proteins with similarity to subunits of the mammalian amiloride-sensitive epithelial Na+ channel (ENaC) that mediates sodium reabsorption in the kidney and lung. mec-4 is expressed exclusively in six neurons that laser ablation studies have identified as gentle-touch receptors, and mec-10 is expressed in these six neurons plus two pairs of touch receptors that are thought to sense harsher touch. The same genetic screens that identified mec-4 and mec-10 identified other genes required for normal touch sensation in the nematode. MEC-5, a novel collagen, and MEC-9, a protein that includes multiple Kunitz-type protease inhibitor repeats and EGF repeats, are extracellular matrix proteins that may interact with MEC-4/MEC-10 channel subunits on the extracellular side of the neuron to help exert gating tension on the channel. Inside the touch receptor, a specialized cytoskeleton is assembled that features 15-protofilament microtubules composed of MEC-12 a-tubulin and MEC-7 b-tubulin subunits. This cytoskeleton may be linked to tether MEC-4/MEC-10 on the intracellular side. When a mutant hyperactivated MEC-4(d) subunit is heterologously expressed in Xenopus oocytes, voltage-independent Na+ currents are produced that can be modulated in both amplitude and properties by two other proteins also identified by genetic screens as required for touch transduction: MEC-2, a stomatin-like protein, and MEC-6, a protein that shares similarity with mammalian paraoxonases. The C. elegans genome encodes 28 members of the MEC-4 and MEC-10 channel family, called the degenerin family. We discuss here the global role of degenerins in mechanosensation, reporting findings on the function of three other degenerins (UNC-8, DEL-1, and UNC-105) in mechanosensitive and stretch-sensitive behaviors in the nematode, and we review studies addressing the role of mammalian homologues in touch sensation.

Original languageEnglish (US)
Title of host publicationTransduction Channels in Sensory Cells
PublisherWiley Blackwell
Pages1-29
Number of pages29
ISBN (Print)9783527603916, 3527308369, 9783527308361
DOIs
StatePublished - Jun 21 2005
Externally publishedYes

Fingerprint

Caenorhabditis elegans
Touch
Degenerin Sodium Channels
Ion Channels
Neurons
Genes
Tubulin
Proteins
Epithelial Sodium Channels
Signal transduction
Gene encoding
Mammals
Amiloride
Cloning
Extracellular Matrix Proteins
Laser ablation
Protease Inhibitors
Cytoskeleton
Epidermal Growth Factor
Bacteria

Keywords

  • C. elegans model system
  • Genetic and molecular analysis of body touch
  • Gentle body touch
  • Mechanosensation
  • Molecular basis of touch sensation
  • Proteins needed for touch transduction
  • Sensory cells
  • Touch receptor neurons
  • Transduction channels

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Bianchi, L., & Driscoll, M. (2005). The Molecular Basis of Touch Sensation As Modeled in Caenorhabditis elegans. In Transduction Channels in Sensory Cells (pp. 1-29). Wiley Blackwell. https://doi.org/10.1002/3527603913.ch1

The Molecular Basis of Touch Sensation As Modeled in Caenorhabditis elegans. / Bianchi, Laura; Driscoll, Monica.

Transduction Channels in Sensory Cells. Wiley Blackwell, 2005. p. 1-29.

Research output: Chapter in Book/Report/Conference proceedingChapter

Bianchi, L & Driscoll, M 2005, The Molecular Basis of Touch Sensation As Modeled in Caenorhabditis elegans. in Transduction Channels in Sensory Cells. Wiley Blackwell, pp. 1-29. https://doi.org/10.1002/3527603913.ch1
Bianchi L, Driscoll M. The Molecular Basis of Touch Sensation As Modeled in Caenorhabditis elegans. In Transduction Channels in Sensory Cells. Wiley Blackwell. 2005. p. 1-29 https://doi.org/10.1002/3527603913.ch1
Bianchi, Laura ; Driscoll, Monica. / The Molecular Basis of Touch Sensation As Modeled in Caenorhabditis elegans. Transduction Channels in Sensory Cells. Wiley Blackwell, 2005. pp. 1-29
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