Role of intracellulare endothelin-converting enzyme-1 (ECE-1) as a regulator of neuropeptide function and signalling in the skin

• Applicant: Professor Dr. Martin Steinhoff
• Subject Area: Dermatology
• Term: from 2005 to 2013
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 14188445

Recent studies indicate that a variety of peptidases play an important part in the control of neurogenic inflammation. We have recently described a new mechanism showing that endothelinconverting enzyme-1 (ECE-1) cleaves and inactivates substance P in acidified endosomes, thereby freeing β-arrestins from the neurokinin 1 receptor (NK1R), which recycles to mediate receptor resensitization or signalling. Thus, peptidases such as ECE-1 may have important implications in the regulation of neurogenic inflammation and neuronal diseases by controlling neuropeptide receptor resensitization. This implicates that inhibitors of ECE-1 may be beneficial for the treatment of inflammation, pain and other neuronal/psychiatric disorders. The aim of this study will be to determine the precise mechanism of how ECE-1 regulates receptor resensitization in detail and investigates the role of ECE-1 in cutaneous inflammation.

• DFG Programme: Research Grants