Tmem27: A cleaved and shed plasma membrane protein that stimulates pancreatic β cell proliferation

• Published in: Cell metabolism 2005-12, Vol.2 (6), p.385-397
• Main Authors: Akpinar, Pinar, Kuwajima, Satoru, Krützfeldt, Jan, Stoffel, Markus
• Format: Article
• Language: English
• Subjects: Animals; Base Sequence; Cell Differentiation; Cell Membrane - metabolism; Cell Proliferation; Cells, Cultured; Cross-Linking Reagents - pharmacology; Dimerization; Dose-Response Relationship, Drug; Epitopes - chemistry; Gene Expression Regulation; Genetic Vectors; Glucose - pharmacology; Glycoproteins - chemistry; Glycosylation; Hepatocyte Nuclear Factor 1-alpha - metabolism; Humans; Hypertrophy; Immunoblotting; Immunohistochemistry; Insulin - metabolism; Insulin Secretion; Insulin-Secreting Cells - cytology; Insulin-Secreting Cells - metabolism; Islets of Langerhans - cytology; Luciferases - metabolism; Membrane Glycoproteins - metabolism; Membrane Glycoproteins - physiology; Mice; Mice, Transgenic; Microscopy, Electron; Microscopy, Fluorescence; Models, Genetic; Models, Statistical; Molecular Sequence Data; Pancreas - cytology; Pancreas - embryology; Plasmids - metabolism; Protein Structure, Tertiary; Reverse Transcriptase Polymerase Chain Reaction; RNA - chemistry; RNA Interference; Sequence Homology, Nucleic Acid; Thymidine - chemistry; Thymidine - metabolism; Time Factors; Transfection
• ISSN: 1550-4131; 1932-7420
• DOI: 10.1016/j.cmet.2005.11.001

The signals and molecular mechanisms that regulate the replication of terminally differentiated β cells are unknown. Here, we report the identification and characterization of transmembrane protein 27 (Tmem27, collectrin) in pancreatic β cells. Expression of Tmem27 is reduced in Tcf1 −/− mice and is increased in islets of mouse models with hypertrophy of the endocrine pancreas. Tmem27 forms dimers and its extracellular domain is glycosylated, cleaved and shed from the plasma membrane of β cells. This cleavage process is β cell specific and does not occur in other cell types. Overexpression of full-length Tmem27, but not the truncated or soluble protein, leads to increased thymidine incorporation, whereas silencing of Tmem27 using RNAi results in a reduction of cell replication. Furthermore, transgenic mice with increased expression of Tmem27 in pancreatic β cells exhibit increased β cell mass. Our results identify a pancreatic β cell transmembrane protein that regulates cell growth of pancreatic islets.