Hippocalcin, new Ca2+ sensor of a ROS-GC subfamily member, ONE-GC, membrane guanylate cyclase transduction system

Abstract

Hippocalcin is a member of the neuronal Ca 2+ sensor protein family. Among its many biochemical functions, its established physiological function is that via neuronal apoptosis inhibitory protein it protects the neurons from Ca 2+ -induced cell death. The precise biochemical mechanism/s through which hippocalcin functions, is not clear. In the present study, a new mechanism by which it functions is defined. The bovine form of hippocalcin (BovHpca) native to the hippocampus has been purified, sequenced, cloned and studied. The findings show that there is the evolutionary conservation of its structure. It is a Ca 2+ -sensor of a variant form of the ROS-GC subfamily of membrane guanylate cyclases, ONE-GC. It senses physiological increments of Ca 2+ with a K 1/2 of 0.5 μM and stimulates ONE-GC or ONE-GC-like membrane guanylate cyclase. The Hpca-modulated ONE-GC-like transduction system exists in the hippocampal neurons. And hippocalcin-modulated ONE-GC transduction system exists in the olfactory receptor neuroepithelium. The Hpca-gene knock out studies demonstrate that the portion of this is about 30% of the total membrane guanylate cyclase transduction system. The findings establish Hpca as a new Ca 2+ sensor modulator of the ROS-GC membrane guanylate cyclase transduction subfamily. They support the concept on universality of the presence and operation of the ROS-GC transduction system in the sensory and sensory-linked neurons. They validate that the ROS-GC transduction system exists in multiple forms. And they provide an additional mechanism by which ROS-GC subfamily acts as a transducer of the Ca 2+ signals originating in the neurons.

Evolutionary Interrelationships and Insights into Molecular Mechanisms of Functional Divergence: An Analysis of Neuronal Calcium Sensor Proteins

“…All the above proteins also modulate the GUCY2F product (ROS-GC2/ RetGC2) in a similar fashion, albeit at differing efficiencies as assessed by fold-change in activity and EC 50 values [39,51]. Frequenin [44] and HPCA [45] activate the olfactory guanylate cyclase (ONE-GC/GC-D) at elevated calcium concentrations; interestingly, so does GCAP1 [41]. VSNL1, on the other hand, activates the product of NPR2B (atrial natriuretic peptide receptor type B/GC-B) [26,42,43].…”

“…Furthermore, this function is most likely conserved all the way from lower eukaryotes to vertebrates. The vertebrate VILIPs all activate mGCs in their calcium-loaded state [27,42,45,46]. If this is the preserved function, the results would indicate that the function would be conserved in lower eukaryotes too.…”

“…modulate mGC activity [26,27,[42][43][44][45][46]. However, in addition to mGC, each member of the VILIP group is known to interact with multiple targets, generating perhaps the most functionally diverse group among the three [21, 22,25].…”

“…The VILIP member in lower organisms is identified as NCS1 and has been included in the alignment ( Figure 3A). All VILIPs that stimulate mGC activity do so in their calcium-loaded state [27,42,45,46]. Information on the residues on the NCS protein that may mediate the function is available only for NCALD: Venkataraman et al [46] have identified residues on NCALD that may be critical for the interaction through a combination of biological assays, peptide competition and direct binding assays.…”

Proteins-markers of placental insufficiency

“…Что касается двух других белков, отсутствующих в околоплодных водах во II триместре нормальной беременности: CDC37-подобного белка, обладающего шаперонной активностью и регулирующего циклин-зависимые киназы [16] и гиппокальцин-подобного белка 1 -считающегося одним из регуляторов рецепторной сигнальной трансдукции [17], то причины их появления при ПН и участие в механизмах развития этого гестационного осложнения на данном этапе пока трудно объяснимы.…”