Inferiority complex: why do sensory ion channels multimerize?

Abstract

Peripheral somatosensory nerves are equipped with versatile molecular sensors which respond to acute changes in the physical environment. Most of these sensors are ion channels that, when activated, depolarize the sensory nerve terminal causing it to generate action potentials, which is the first step in generation of most somatic sensations, including pain. The activation and inactivation of sensory ion channels is tightly regulated and modulated by a variety of mechanisms. Amongst such mechanisms is the regulation of sensory ion channel activity via direct molecular interactions with other proteins in multi-protein complexes at the plasma membrane of sensory nerve terminals. In this brief review, we will consider several examples of such complexes formed around a prototypic sensory receptor, transient receptor potential vanilloid type 1 (TRPV1). We will also discuss some inherent conceptual difficulties arising from the multitude of reported complexes.

Keywords: G-protein-coupled receptors; TRPV1; nociception; pain; sensory neurons.

Figure 1.. Overview of TRPV1-containing complexes and their localization along the peripheral somatosensory pathway.

TRPV1–TRPA1 (A), TRPV1–ANO1 (B), TRPV1–GABA_B (C), and TRPV1–AKAP79/150 ‘supercomplex’ (D) are shown. Localization of complexes at various compartments (peripheral terminal, axon, soma, presynaptic terminal in the dorsal spinal cord) of the peripheral sensory neuron are shown with the corresponding letter for each complex, colour-coded to show level of evidence for expression at a specific compartment.

Figure 2.. Association of a sensory ion channel into complexes with multiple different partners: two possible scenarios.

(A) A principal sensory channel (red) forms individual complexes with other partner ion channels or regulatory proteins; each complex behaves independently. (B) A principal sensory channel forms a ‘supercomplex’ with multiple other partner channels/proteins.