Calcium-modulated ciliary membrane guanylate cyclase transduction machinery: Constitution and operational principles

Abstract

Odorant transduction is a biochemical process by which the odorant signal generates the electric signal. The cilia of the olfactory neuroepithelium are the sites of this process. This study documents the detailed biochemical, structural and functional description of an odorant-responsive Ca2+ -modulated membrane guanylate cyclase transduction machinery in the cilia. Myristoylated (myr)-neurocalcin delta is the Ca2+ -sensor component and the cyclase, ONE-GC, the transduction component of the machinery. Myr-neurocalcin delta senses increments in free Ca2+, binds to a defined domain of ONE-GC and stimulates the cyclase. The findings enable the formulation of an odorant transduction model in which three pivotal signaling components--Ca2+, myr-neurocalcin delta and ONE-GC--of the transduction machinery are locked. A glaring feature of the model is that its Ca2+ -dependent operational principle is opposite to the phototransduction model.

Neuronal Ca2+ sensor protein VILIP-1 affects cGMP signalling of guanylyl cyclase B by regulating clathrin-dependent receptor recycling in hippocampal neurons

“…Interestingly, these data were recently supported by findings that the related protein neurocalcin δ was found to interact with and directly influence related guanylyl cyclases, namely the retinal and the olfactory GCs Duda et al, 2004). However, we have not found the same direct activation mechanism, although VILIP-1 can interact in a Ca 2+ -dependent manner with the cytosolic catalytic domains of the cell surface receptors GC-A and GC-B in vitro .…”

S100B‐modulated Ca2+‐dependent ROS‐GC1 transduction machinery in the gustatory epithelium: a new mechanism in gustatory transduction

“…4B, lane ''-Ca 2þ ''). This is probably due to the presence of the residual Ca 2þ concentration in the membranes, as has been observed earlier for the neurocalcin d/ROS-GC1 complex in the inner plexiform layer of the retinal neurons [26] and for the neurocalcin d/ONE-GC complex in the cilia of the olfactory neurons [36]. Another possibility is that once S100B binds ROS-GC1, it remains bound to the cyclase even in the absence of Ca 2þ as has been observed with other intracellular targets of S100B [43,44].…”

“…In the semi to the micromolar range of free Ca 2þ , both are stimulated by S100B, and ROS-GC1 also by neurocalcin d (reviewed in: [26,28,34]). ONE-GC is only stimulated, and not inhibited, by free Ca 2þ when accompanied by neurocalcin d [36,37]. To determine which one of these cyclases is functionally expressed in the gustatory epithelium, individual aliquots of the membranes were incubated with the recombinant forms of GCAP1, GCAP2, S100B, or neurocalcin d in the presence of the appropriate concentration of free Ca 2þ .…”

“…Other forms are defined by the composition of its two components: the Ca 2þ -sensor protein and the transducer enzyme ROS-GC (reviewed in: [26][27][28][34][35][36]45]). There are three forms of ROS-GC: ROS-GC1, ROS-GC2, and ONE-GC (also named as ret-GC1, ret-GC2 and GC-D); and four forms of the Ca 2þ -sensor proteins: GCAP1 [38], GCAP2 [45], S100B [39,40] and neurocalcin d [26,30,36]. Thus, theoretically, with the individual pairing of a sensor protein with a ROS-GC, the machine can exist in 12 different forms.…”

“…Each of the guanylate cyclases has a defined target domain for its sensor protein. Analysis of the sensory model systems of vision, olfaction and the pinealocytes has revealed that in the rod outer segments of the photoreceptors, ROS-GC transduction machine's composition is one molecule of GCAP1 and one molecule of GCAP2 with one ROS-GC1 dimer molecule [46]; separately in the two different forms of the pinealocytes it exists as GCAP1/ROS-GC1 or S100B/ROS-GC1 [31]; in the olfactory sensory neurons (cilia), it exists with the pairing of neurocalcin d/ONE-GC [36,37]; and in the mitral cells of the olfactory bulb it exists as GCAP1/ROS-GC1 [32]. These examples indicate that how with its change in composition, the transduction machinery achieves universality, cellular specificity and complete reversibility in its operation by a wide variety of Ca 2þ signals generated in the neurosensory and the neurosensory-linked neurons.…”