Abstract
D-aspartate (D-Asp) is found in specific neurons, transported to neuronal terminals and released in a stimulation-dependent manner. Because D-Asp formation is not well understood, determining its function has proved challenging. Significant levels of D-Asp are present in the cerebral ganglion of the F- and C-clusters of the invertebrate Aplysia californica, and D-Asp appears to be involved in cell-cell communication in this system. Here, we describe a novel protein, DAR1, from A. californica that can convert aspartate and serine to their other chiral form in a pyridoxal 5'-phosphate (PLP)-dependent manner. DAR1 has a predicted length of 325 amino acids and is 55% identical to the bivalve aspartate racemase, EC 5.1.1.13, and 41% identical to the mammalian serine racemase, EC 5.1.1.18. However, it is only 14% identical to the recently reported mammalian aspartate racemase, DR, which is closely related to glutamate-oxaloacetate transaminase, EC 2.6.1.1. Using whole-mount immunohistochemistry staining of the A. californica central nervous system, we localized DAR1-like immunoreactivity to the medial region of the cerebral ganglion where the F- and C-clusters are situated. The biochemical and functional similarities between DAR1 and other animal serine and aspartate racemases make it valuable for examining PLP-dependent racemases, promising to increase our knowledge of enzyme regulation and ultimately, D-serine and D-Asp signaling pathways.
Highlights
Degraded by D-amino acid oxidase (DAO) [4] and acts as a novel glial neurotransmitter/neuromodulator [5, 6]
The enzyme required for the biosynthesis of D-Asp in the brain was not identified until recently, when the first mammalian aspartate racemase, distinct aspartate racemase (DR), was cloned and characterized [13], how much this enzyme accounts for overall D-Asp synthesis is unclear
We have isolated a novel racemase from A. californica neuronal tissues, characterized its biochemical features, and validated its ability to form D-Asp and D-Ser
Summary
Degraded by D-amino acid oxidase (DAO) [4] and acts as a novel glial neurotransmitter/neuromodulator [5, 6]. In contrast to D-Ser, D-Asp is widely distributed in animals It has been found in the brain, retina, and endocrine and exocrine tissues of both vertebrates and invertebrates [10]. The D-Ser biosynthesis pathway was described in 1999 [3], as noted, DR, the first D-Asp racemase enzyme from the animal brain, was just recently reported [13]. The only invertebrate Asp racemase described, SbAspR, was isolated from the foot muscle of the bivalve Scapharca broughtonii [23]. It is unknown if the enzyme is present in bivalve nervous and endocrine systems. We observed enzyme activity in the cerebral ganglion that could transfer [14C] from L-Asp to D-Asp in radioisotope pulse-and-chase experiments
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