Cysteine Sulfinate Decarboxylase (CSD): Molecular Cloning, Sequence and Genomic Expression in Brain

Abstract

Cysteine sulfinate decarboxylase (CSD) is thought to be the rate limiting step of taurine biosynthesis⁹. It may thus represent a key enzyme in the function of taurine. While a CSD activity was detected in crude brain extracts more than four decades ago, its identification, characterization and cellular localization in brain proved difficult and led to controversial reports (For review see^14,15). We previously established that there exists in brain an enzyme showing a strong affinity and narrow specificity for cysteine sulfinic acid (CSA) and cysteic acid (CA)⁶. Brain CSD appeared to be very similar to the CSD from liver: both proteins have similar physico-chemical and enzymatic properties^3,6 and share common antigenic epitopes⁹. Using a specific antiserum against liver CSD¹ we showed that CSD immunopositive cells in hippocampus and cerebellum were astrocytes through a quantitative double immunofluorescence analysis with appropriate astroglial markers¹¹. In rat brain, CSD expression level reveals two distinct phenotypes in astrocytes that exhibit a different distribution pattern¹⁰. Given that taurine was reported to be localized predominantly in neurons^5,8, our findings suggest that the poorly understood functional role of taurine in the brain^4,7 should be investigated within the framework of astrocyte-neuron interactions. In addition, our results suggest that the CSD expression level may vary greatly among astrocytes according to their location and functional state. Disclosing the regulation of the genomic expression of CSD in various experimental situations could help provide insight into the physiological role of taurine in the brain. With this long-term goal in mind, we have carried out molecular cloning of CSD¹², determined its sequence and developed new appropriate tools, such as the quantification of CSD-mRNA through competitive reverse transcription coupled with polymerase chain reaction (RT-PCR). These molecular biology techniques will enable us to investigate the regulation of the genomic expression of CSD in brain, as well as in astrocytes in primary culture.