Histatin-1 is an endogenous ligand of the sigma-2 receptor

Kyung No Son, Hyun Lee, Dhara Shah, Sushma Kalmodia, Ryan Cree Miller, Marwan Ali, Arun Balasubramaniam, Stephanie M. Cologna, Hyunjoon Kong, Deepak Shukla, Vinay Kumar Aakalu

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish (US)
Pages (from-to)6815-6827
Number of pages13
JournalFEBS Journal
Issue number23
StatePublished - Dec 2021


  • antimicrobial peptide
  • histatin-1
  • MAC30
  • migration
  • sigma-2 receptor
  • TMEM97
  • wound healing

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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