Cathepsin H functions as an aminopeptidase in secretory vesicles for production of enkephalin and galanin peptide neurotransmitters.

Journal of Neurochemistry
Weiya Douglas LuVivian Y H Hook

Abstract

Peptide neurotransmitters function as key intercellular signaling molecules in the nervous system. These peptides are generated in secretory vesicles from proneuropeptides by proteolytic processing at dibasic residues, followed by removal of N- and/or C-terminal basic residues to form active peptides. Enkephalin biosynthesis from proenkephalin utilizes the cysteine protease cathepsin L and the subtilisin-like prohormone convertase 2 (PC2). Cathepsin L generates peptide intermediates with N-terminal basic residue extensions, which must be removed by an aminopeptidase. In this study, we identified cathepsin H as an aminopeptidase in secretory vesicles that produces (Met)enkephalin (ME) by sequential removal of basic residues from KR-ME and KK-ME, supported by in vivo knockout of the cathepsin H gene. Localization of cathepsin H in secretory vesicles was demonstrated by immunoelectron microscopy and immunofluorescence deconvolution microscopy. Purified human cathepsin H sequentially removes N-terminal basic residues to generate ME, with peptide products characterized by nano-LC-MS/MS tandem mass spectrometry. Cathepsin H shows highest activities for cleaving N-terminal basic residues (Arg and Lys) among amino acid fluorogenic subs...Continue Reading

References

Dec 15, 1992·European Journal of Biochemistry·M Rothe, J Dodt
Jan 1, 1988·Annual Review of Physiology·L D Fricker
Jun 3, 2000·Annual Review of Pharmacology and Toxicology·P Y LawH H Loh
Mar 22, 2001·Proceedings of the National Academy of Sciences of the United States of America·R A SteinerJ N Crawley
Jul 19, 2003·Proceedings of the National Academy of Sciences of the United States of America·Sukkid YasothornsrikulVivian Hook
May 7, 2004·Peptides·Pika Mesko BrguljanTatjana Popovic
Apr 7, 2005·Behavioral and Cognitive Neuroscience Reviews·John K Robinson
Oct 3, 2006·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Nathalie ScamuffaAbdel-Majid Khatib
Jan 11, 2008·Annual Review of Pharmacology and Toxicology·Vivian HookShin-Rong Hwang
Mar 18, 2008·The International Journal of Biochemistry & Cell Biology·Nabil G SeidahAnnik Prat
Jul 11, 2008·Neuron·George F Koob
Oct 20, 2009·Molecular and Cellular Neurosciences·Ardalan MinokadehVivian Hook
May 4, 2010·The Journal of Biological Chemistry·Michael E D'AngeloVivien R Sutton
Mar 29, 2011·Pharmacology & Therapeutics·Lei ZhangHerbert Herzog
Aug 9, 2011·Bioinformatics·Yoona KimNuno Bandeira
Mar 1, 1993·Journal of Microscopy·E M M MandersJ A Aten

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Citations

Oct 16, 2013·Peptides·Richard J Bodnar
Nov 16, 2013·Molecular Neurobiology·Anja Pišlar, Janko Kos
Jul 2, 2014·Proceedings of the National Academy of Sciences of the United States of America·Tina FløyelFlemming Pociot
Dec 8, 2016·The FEBS Journal·Stephanie KettererThomas Reinheckel
Aug 15, 2019·American Journal of Respiratory and Critical Care Medicine·Robin R DeterdingEmily M DeBoer
Jun 1, 2013·Biomolecular Concepts·Marko Novinec, Brigita Lenarčič
Feb 5, 2021·ACS Chemical Biology·Md Shadman Ridwan AbidJames W Checco
Apr 19, 2018·Journal of the American Society for Mass Spectrometry·Vivian HookOliver Fiehn

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