Study on the role of extracellular deubiquitinating enzymes

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We aimed to elucidate the biological role of extracellular UCH-L1. To achieve this purpose, we used cultured cells and studied whether the protein was secreted or not into the media. We observed that UCH-L1 was secreted into the media via a unconventional pathway. Interestingly, exosome contained UCH-L1. I93M UCH-L1 mutant was less secreted compared with wild type of UCH-L1. Then we studied a possible interaction of UCH-L1 with other disease-related proteins in the secretory event. We found that the secretion of UCH-L1 was modified by the presence of mutated alpha-synuclein and huntingtin. These results suggest that secretion of UCH-L1 into extracellular space might be related to the pathophysiological conditions of neurodegenerative disorders.