PUBLICATION
BefA, a microbiota-secreted membrane disrupter, disseminates to the pancreas and increases β cell mass
- Authors
- Hill, J.H., Massaquoi, M.S., Sweeney, E.G., Wall, E.S., Jahl, P., Bell, R., Kallio, K., Derrick, D., Murtaugh, L.C., Parthasarathy, R., Remington, S.J., Round, J.L., Guillemin, K.
- ID
- ZDB-PUB-221018-74
- Date
- 2022
- Source
- Cell Metabolism 34(11): 1779-1791.e9 (Journal)
- Registered Authors
- Guillemin, Karen
- Keywords
- BefA, SYLF domain, diabetes, membrane permeabilization, microbiota, β cell proliferation
- MeSH Terms
-
- Proteins/metabolism
- Animals
- Microbiota*
- Zebrafish
- Insulin/metabolism
- PubMed
- 36240759 Full text @ Cell Metab.
Abstract
Microbiome dysbiosis is a feature of diabetes, but how microbial products influence insulin production is poorly understood. We report the mechanism of BefA, a microbiome-derived protein that increases proliferation of insulin-producing β cells during development in gnotobiotic zebrafish and mice. BefA disseminates systemically by multiple anatomic routes to act directly on pancreatic islets. We detail BefA's atomic structure, containing a lipid-binding SYLF domain, and demonstrate that it permeabilizes synthetic liposomes and bacterial membranes. A BefA mutant impaired in membrane disruption fails to expand β cells, whereas the pore-forming host defense protein, Reg3, stimulates β cell proliferation. Our work demonstrates that membrane permeabilization by microbiome-derived and host defense proteins is necessary and sufficient for β cell expansion during pancreas development, potentially connecting microbiome composition with diabetes risk.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping