@article{61106bcea1ea4250a19ccdee8a1bd58d,
title = "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.",
keywords = "antimicrobial peptide, histatin-1, MAC30, migration, sigma-2 receptor, TMEM97, wound healing",
author = "Son, {Kyung No} and Hyun Lee and Dhara Shah and Sushma Kalmodia and Miller, {Ryan Cree} and Marwan Ali and Arun Balasubramaniam and Cologna, {Stephanie M.} and Hyunjoon Kong and Deepak Shukla and Aakalu, {Vinay Kumar}",
note = "Funding Information: Portions of this work were carried out in the Protein Core and Biophysics Core of the Research Resources Center at the University of Illinois at Chicago. Special thanks to Lasanthi Jayathilaka PhD for her peptide synthesis expertise. Additional thanks to Melissa R. Pergande for work on the proteomics analysis. determinations and receptor binding profiles were generously provided by the National Institute of Mental Health's Psychoactive Drug Screening Program (PDSP), Contract # HHSN‐271‐2018‐00023‐C (NIMH PDSP). The NIMH PDSP is directed by Bryan L. Roth MD, PhD at the University of North Carolina at Chapel Hill and Project Officer Jamie Driscoll at NIMH, Bethesda MD, USA. VKA acknowledges grant funding from: (a) National Eye Institute, NIH (USA): K08EY024339, R01EY029409, P30EY001792. (b) Department of Defense (USA): W81XWH‐17‐1‐0122. (c) Veterans Affairs Office of Research and Development (USA): I01BX004080. (d) Research to Prevent Blindness, New York, NY (USA). DS acknowledges grant funding from: (a) National Eye Institute, NIH (USA) P30EY001792, R01EY024710. (b) Research to Prevent Blindness, New York, NY. SMC acknowledges grant funding from: (a) Together Strong‐NPC Foundation. (b) National Institutes of Health, National Institute of Neurological Disorders and Stroke/National Institute on Aging R01 NS114413 Ki Publisher Copyright: {\textcopyright} 2021 Federation of European Biochemical Societies",
year = "2021",
month = dec,
doi = "10.1111/febs.16108",
language = "English (US)",
volume = "288",
pages = "6815--6827",
journal = "FEBS Journal",
issn = "1742-464X",
publisher = "Wiley-Blackwell",
number = "23",
}