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
-
- Animals
- Diabetes Mellitus*/metabolism
- Insulin/metabolism
- Mice
- Microbiota*
- Pancreas/metabolism
- Proteins/metabolism
- Zebrafish
- PubMed
- 36240759 Full text @ Cell Metab.
Citation
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. (2022) BefA, a microbiota-secreted membrane disrupter, disseminates to the pancreas and increases β cell mass. Cell Metabolism. 34(11):1779-1791.e9.
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