Abstract
Dynamic changes in somatosensory perception occur as a result of multiple signaling events. In many instances, over-activation of sensory receptors results in the desensitization and subsequent increased threshold for activation of receptors. In other cases, receptor sensitization can occur following tissue injury and/or inflammation. In both cases, signaling mechanisms that control alterations in receptor activities can significantly affect organism response to sensory stimuli, including thermal, mechanical, and chemical. Due to the homeostatic nature of somatosensory recognition, dynamic changes in receptor response can negatively affect an individual's way of life, as well as alert individuals to tissue damage. Here, we will focus on scaffolding structures that regulate somatosensory neuronal excitability.
Highlights
Dynamic changes in somatosensory perception occur as a result of multiple signaling events
The majority of proteins that belong to the Homer family share two structurally conserved features in their secondary form: an N-terminal enabled/vasodilatorstimulated phosphoprotein homology 1 (EVH1) domain responsible for associating with proline-rich sequences contained within its target/ligand proteins, and a C-terminal coiled-coil domain containing multiple leucine zipper motifs that control homo/heteromerization of Homer proteins (Xiao et al, 1998; Tadokoro et al, 1999)
One short Homer protein splice variant, Homer1A, does not contain this C-terminal region (Brakeman et al, 1997), allowing it to exist as a dominant-negative inhibitor to the scaffolding functions of the long forms
Summary
Departments of Oral and Maxillofacial Surgery, Pharmacology, University of Texas Health Science Center at San Antonio, TX, USA. Receptor sensitization can occur following tissue injury and/or inflammation In both cases, signaling mechanisms that control alterations in receptor activities can significantly affect organism response to sensory stimuli, including thermal, mechanical, and chemical. Biochemical reactions that modify receptor response posttranslationally are often governed by protein-protein or proteinlipid interactions In many cases, these reactions are dependent upon substrate/effector proximity, influencing the catalytic conditions required for a biochemical reaction to occur. We will discuss certain groups of scaffolding structures that directly associate with and indirectly modify somatosensory receptors responsible for transducing environmental changes to the nervous system. The shortened splice variant Homer1A and its dominantnegative ability to associate with target proteins but not scaffold additional Homer proteins, has been demonstrated to be an important mediator of peripheral pain. Short hairpin RNA (shRNA) designed to knock-down Homer1A
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