Student Theses and Dissertations
Date of Award
2006
Document Type
Thesis
RU Laboratory
Stoffel Laboratory
Keywords
pancreas development, diabetes mellitus, pancreatic beta cells, transmembrane protein 27
Abstract
The signals and the molecular mechanisms that regulate the replication of terminally differentiated β cells are unclear. In this thesis I report the identification of a gene encoding transmembrane protein 27 (TMEM27) in pancreatic β cells. Expression of Tmem27 is reduced in Tcf1–/– mice, which exhibit defects in proliferation, and is increased in islets of ob/ob, db/db and aP2- Srebp-1c transgenic mice with marked hypertrophy of the endocrine pancreas. Tmem27 is expressed in hormone positive cells at early stages of pancreas development and becomes restricted to pancreatic β cells in the mature pancreas. Biochemical characterization revealed that the Tmem27 exists as a dimer and that its extracellular domain is glycosylated, cleaved and shed from the plasma membrane. The cleavage process of Tmem27 is β cell-specific and does not occur in other cell types. Overexpression of full-length Tmem27, but not the truncated or soluble protein, in MIN6 cells 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 compared to their control littermates. The following results identify a novel pancreatic β cell-shed protein that regulates cell growth of pancreatic islets.
Permanent URL
http://hdl.handle.net/10209/113
Recommended Citation
Akpinar, Pinar, "TMEM27: A Cleaved and Shed Plasma Membrane Protein That Stimulates Pancreatic Beta Cell Proliferation" (2006). Student Theses and Dissertations. 2.
https://digitalcommons.rockefeller.edu/student_theses_and_dissertations/2
Comments
A thesis presented to the faculty of The Rockefeller University in partial fulfillment of the requirements for the degree of Doctor of Philosophy.