Histatin-1 is an endogenous ligand of the sigma-2 receptor. FEBS J 2021 Dec;288(23):6815-6827
Date
07/08/2021Pubmed ID
34233061Pubmed Central ID
PMC8648968DOI
10.1111/febs.16108Scopus ID
2-s2.0-85111060731 (requires institutional sign-in at Scopus site) 14 CitationsAbstract
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.
Author List
Son KN, Lee H, Shah D, Kalmodia S, Miller RC, Ali M, Balasubramaniam A, Cologna SM, Kong H, Shukla D, Aakalu VKAuthor
Vinay Kumar Aakalu MPH, MD Chair, Professor in the Ophthalmology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Amino Acid SequenceCell Membrane
Cell Movement
Cells, Cultured
Epithelial Cells
Epithelium, Corneal
HEK293 Cells
HeLa Cells
Histatins
Humans
Ligands
Membrane Proteins
Microscopy, Confocal
Protein Binding
Radioligand Assay
Receptors, sigma
