Molecular anatomy and physiology of exocytosis in sensory hair cells

Cell Calcium. 2012 Sep-Oct;52(3-4):327-37. doi: 10.1016/j.ceca.2012.05.008. Epub 2012 Jun 6.

Abstract

Hair cells mediate our senses of hearing and balance by synaptic release of glutamate from somatic active zones (AZs). They share conserved mechanisms of exocytosis with neurons and other secretory cells of diverse form and function. Concurrently, AZs of these neuro-epithelial hair cells employ several processes that differ remarkably from those of neuronal synaptic terminals of the brain. Their unique molecular anatomy enables them to better respond to small, graded changes in membrane potential and to produce unsurpassed rates of exocytosis. Here, we focus on the AZs of cochlear inner hair cells (IHCs). As in other hair cells, these AZs are occupied by a cytoplasmic extension of the presynaptic density, called the synaptic ribbon: a specialized protein complex required for normal physiological function. Some proteins found at IHC synapses are uniquely expressed or enriched there, where their disruption can beget deafness in humans and in animal models. Other proteins, essential for regulation of conventional neuronal Ca(2+)-triggered fusion, are apparently absent from IHCs. Certain common synaptic proteins appear to have extra significance at ribbon-type AZs because of their interactions with unique molecules, their unusual concentrations, or their atypical localization and regulation. We summarize the molecular-anatomical specializations that underlie the unique synaptic physiology of hair cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alcohol Oxidoreductases / metabolism
  • Animals
  • Calcium Channels, L-Type / metabolism
  • Co-Repressor Proteins
  • Cytoskeletal Proteins / metabolism
  • Exocytosis / physiology*
  • Hair Cells, Auditory / metabolism*
  • Hippocampus / cytology
  • Hippocampus / metabolism
  • Membrane Proteins / metabolism
  • Mice
  • Nerve Tissue Proteins / metabolism
  • SNARE Proteins / metabolism
  • Synapses / metabolism
  • Synaptic Transmission / physiology
  • Synaptic Vesicles / metabolism
  • Synaptotagmins / metabolism

Substances

  • Cacna1d protein, mouse
  • Calcium Channels, L-Type
  • Co-Repressor Proteins
  • Cytoskeletal Proteins
  • Membrane Proteins
  • Nerve Tissue Proteins
  • SNARE Proteins
  • otoferlin protein, mouse
  • Synaptotagmins
  • Alcohol Oxidoreductases
  • CTBP2 protein, human