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Histatin‐1 is an endogenous ligand of the sigma‐2 receptor
Abstract
The Sigma‐2 receptor (S2R) (a.k.a TMEM97) is an important endoplasmic reticular protein involved in cancer, cholesterol processing, cell migration, and neurodegenerative diseases, including Niemann–Pick Type C. While several S2R pharmacologic agents have been discovered, its recent (2017) cloning has limited biological investigation, and no endogenous ligands of the S2R are known. Histatins are a family of endogenous antimicrobial peptides that have numerous important effects in multiple biological systems, including antifungal, antibacterial, cancer pathogenesis, immunomodulation, and wound healing. Histatin‐1 (Hst1) has important roles in epithelial wound healing and cell migration, and is the primary wound healing agent in saliva. Little is understood about the downstream machinery that underpins the effects of histatins, and no mammalian receptor is known to date. In this study, we show, using biophysical methods and functional assays, that Hst1 is an endogenous ligand for S2R and that S2R is a mammalian receptor for Hst1.
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The functional binding of histatin-1 to S2R was confirmed in human corneal epithelial cells.
“Histatin-1 is also found in human tears [111], and the functional binding of histatin-1 to S2R was confirmed in human corneal epithelial cells [80].”
From Sigma-2 Receptors—From Basic Biology to Therapeutic Target: A Focus on Age-Related Degenerative Diseases (2023) · cites this paper as [80]
Two putative endogenous ligands of S2R have been identified: histatin-1 and the oxysterol 20(S)-OHC.
“In 2021, two studies were published that identified two putative endogenous ligands of S2R: histatin-1 [80] and the oxysterol 20(S)-OHC [81].”
From Sigma-2 Receptors—From Basic Biology to Therapeutic Target: A Focus on Age-Related Degenerative Diseases (2023) · cites this paper as [80]
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Lizama, B. N., Kahle, J., Catalano, S. M., Caggiano, A. O., Grundman, M., & Hamby, M. E. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24076251 · Cited by 54
Metadata
- Authors
- Son, K., Lee, H., Shah, D., Kalmodia, S., Miller, R. C., Ali, M., Balasubramaniam, A., Cologna, S. M., Kong, H., Shukla, D., & Aakalu, V. K.
- Affiliations
- Department of Ophthalmology and Visual Sciences University of Illinois at Chicago IL USA
- Department of Pharmaceutical Science and Biophysics Core at Research Resources Center University of Illinois at Chicago IL USA
- Department of Chemical & Biomolecular Engineering University of Illinois at Urbana‐Champaign IL USA
- Department of Chemistry University of Illinois at Chicago IL USA
- ORCID
- Aakalu, Vinay Kumar
- Venue
- The FEBS Journal
- Publisher
- Wiley
- Published
- 2021-07-23
- Volume
- 288
- Issue
- 23
- Pages
- 6815-6827
- ISSN
- 1742-464X
- 1742-4658
- PMC
- PMC8648968
- Cited by
- 16
- References
- 2
- Language
- en
- Licence
- Funders
- National Eye Institute (R01EY029409, K08EY024339, P30EY001792, R01EY024710)
- Congressionally Directed Medical Research Programs (W81XWH‐17‐1‐0122)
- Office of Research and Development (I01BX004080)
- National Institute of Neurological Disorders and Stroke (R01 NS114413)
- Research to Prevent Blindness
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