| First Author | Minokadeh A | Year | 2010 |
| Journal | Mol Cell Neurosci | Volume | 43 |
| Issue | 1 | Pages | 98-107 |
| PubMed ID | 19837164 | Mgi Jnum | J:158324 |
| Mgi Id | MGI:4438546 | Doi | 10.1016/j.mcn.2009.10.001 |
| Citation | Minokadeh A, et al. (2010) Cathepsin L participates in dynorphin production in brain cortex, illustrated by protease gene knockout and expression. Mol Cell Neurosci 43(1):98-107 |
| abstractText | Dynorphin opioid neuropeptides mediate neurotransmission for analgesia and behavioral functions. Dynorphin A, dynorphin B, and alpha-neoendorphin are generated from prodynorphin by proteolytic processing. This study demonstrates the significant role of the cysteine protease cathepsin L for producing dynorphins. Cathepsin L knockout mouse brains showed extensive decreases in dynorphin A, dynorphin B, and alpha-neoendorphin that were reduced by 75%, 83%, and 90%, respectively, compared to controls. Moreover, cathepsin L in brain cortical neurons was colocalized with dynorphins in secretory vesicles, the primary site of neuropeptide production. Cellular coexpression of cathepsin L with prodynorphin in PC12 cells resulted in increased production of dynorphins A and B. Comparative studies of PC1/3 and PC2 convertases showed that PC1/3 knockout mouse brains had a modest decrease in dynorphin A, and PC2 knockout mice showed a minor decrease in alpha-neoendorphin. Overall, these results demonstrate a prominent role for cathepsin L, jointly with PC1/3 and PC2, for production of dynorphins in brain. |
