The observed diverse spatial distribution among harmonin isoforms in subcellular compartments of photoreceptor cells may reflect differences between harmonin isoforms in their cellular function and their involvement in supramolecular protein complexes. In these compartments, harmonin is associated with membrane specializations, the outer segment disks, or the membrane ribbon synapses, as has been shown for other scaffold proteins containing PDZ modules.
5 Because the known binding partners of harmonin to its PDZ domains, myosin VIIa and cadherin 23, are not present in the outer segment, harmonin may be targeted to this region of the photoreceptor by other binding partners. In signal transduction compartments of other sensory systems, PDZ domain–containing scaffold proteins coordinate the organization of signaling molecules into macromolecular complexes (transducisomes) providing specificity, sensitivity, and speed in intracellular signaling pathways.
30 31 In the rhabdomeric photoreceptors of the invertebrate animal model
Drosophila melanogaster, the PDZ protein inactivation no afterpotential D (INAD) clusters the components of the visual signal transduction cascade into a signal complex.
32 There is a growing body of evidence that suggests transduction cascades in vertebrates may also be arranged in signaling complexes.
33 34 We recently confirmed this hypothesis by demonstrating that harmonin organizes protein complexes in stereovilli,
13 the apical specializations for signal transduction of vertebrate hair cells.
35 The identification of proteins of the photoreceptor outer segment interacting with the PDZ domains of harmonin should further reveal the role of harmonin in the organization of signal complexes in vertebrates. As in the transducisome of the microvilli of
Drosophila rhabdomeres, a putative protein complex of vertebrate photoreceptor outer segments is probably associated with the actin cytoskeleton. Our present study revealed that harmonin b isoforms are also expressed in photoreceptor outer segments. We have shown previously that the PST domain found in b isoforms, but not in a or c, can bind directly to actin filaments.
13 Previous studies have indicated the presence of an actin cytoskeleton in photoreceptor outer segments.
36 37 Thus, we propose that harmonin b may interact with this outer segment actin cytoskeleton, and, in consequence, harmonin may bridge a putative protein complex composed of the outer segment proteins binding to its PDZ domains to the actin cytoskeleton.