Lysosomal Cathepsin A Plays a Significant Role in the Processing of Endogenous Bioactive Peptides
Open accessAbstract
Lysosomal serine carboxypeptidase Cathepsin A (CTSA) is a multifunctional enzyme with distinct protective and catalytic function. CTSA that is present in the lysosomal multienzyme complex facilitates correct lysosomal routing, stability and activation of betagalactosidase and alpha-neuraminidase. In addition, CTSA plays a role in the inactivation of bioactive peptides including bradykinin, substances P, oxytocin, angiotensin I and endothelin-I by cleavage of one or two amino acid(s) from the C-terminal ends. In this study, we aimed to elucidate the regulatory role of CTSA on bioactive peptides in a knock-in mouse model of CTSAS190A. We evaluated the levels of bradykinin, substances P, oxytocin, angiotensin I and endothelin-I in the kidney, liver, lung, brain and serum of the CTSAS190A mouse model at three- and six-months of age. Our results suggest that CTSA selectively contributes to the processing of bioactive peptides in different tissues of CTSAS190A mice compared to those of age-matched wild-type mice.
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CTSA is primarily localized to lysosomes.
“Although CTSA is primarily localized to lysosomes, a fraction of CTSA can also be secreted, where it may have further roles in extracellular protein processing and signalling 30 .”
From Dietary cholesterol activates a Ral-dependent pathway driving LDLR turnover (2026) · cites this paper as [30]
A fraction of CTSA can be secreted.
“Although CTSA is primarily localized to lysosomes, a fraction of CTSA can also be secreted, where it may have further roles in extracellular protein processing and signalling 30 .”
From Dietary cholesterol activates a Ral-dependent pathway driving LDLR turnover (2026) · cites this paper as [30]
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Cathepsins: Proteases that are vital for survival but can also be fatal
Patel, S., Homaei, A., El-Seedi, H. R., & Akhtar, N. (2018) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2018.05.148 · Cited by 224 · see citing works
Dietary cholesterol activates a Ral-dependent pathway driving LDLR turnover
Feng, X., Zhang, S., Wang, Y., Kurlagunda, T., Sit, A., Jaishankar, P., Yang, P., Sakane, S., Park, S. Y., Wisessaowapak, C., et al. (2026) · Nature · doi:10.1038/s41586-026-10697-z · Cited by 2 · see citing works
- Authors
- Timur, Z. K., Akyildiz Demir, S., & Seyrantepe, V.
- Affiliations
- Izmir Institute of Technology (TR)
- Corresponding author
- Seyrantepe, Volkan
- ORCID
- Seyrantepe, Volkan
- Venue
- Frontiers in Molecular Biosciences
- Publisher
- Frontiers Media SA
- Published
- 2016-10-25
- Volume
- 3
- Pages
- 68-68
- ISSN
- 2296-889X (ISSN-L)
- PMC
- PMC5078471
- OpenAlex
- W2532004191
- Cited by
- 38
- References
- 1
- Citations by year
- 2026: 4 · 2025: 2 · 2024: 4 · 2023: 5 · 2022: 8 · 2021: 2 · 2020: 6 · 2019: 3 · 2018: 2 · 2017: 1 · 2016: 1
- FWCI
- 1.43
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Frontiers in Molecular Biosciences (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- İYTE (İZMİR YÜKSEK TEKNOLOJİ ENSTİTÜSÜ) (submittedVersion, other-oa)
- IYTE GCRIS Database (Izmir Institute of Technology) (submittedVersion, other-oa)
- Funders
- Türkiye Bilimsel ve Teknolojik Araştirma Kurumu (111T896)
- Topics
- Health Sciences › Medicine › Genetics › Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Protease and Inhibitor Mechanisms
- Health Sciences › Medicine › Oncology › Peptidase Inhibition and Analysis
- Keywords
- cathepsin A, bradykinin, substance P, oxytocin, angiotensin I, endothelin-1, C-terminal cleavage
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