Premium
ICA 512, an autoantigen of type I diabetes, is an intrinsic membrane protein of neurosecretory granules.
Author(s) -
Solimena M.,
Dirkx R.,
Hermel J. M.,
PleasicWilliams S.,
Shapiro J. A.,
Caron L.,
Rabin D. U.
Publication year - 1996
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1002/j.1460-2075.1996.tb00564.x
Subject(s) - haven , medicine , mathematics , combinatorics
Islet cell autoantigen (ICA) 512 is a novel autoantigen of insulin‐dependent diabetes mellitus (IDDM) which is homologous to receptor‐type protein tyrosine phosphatases (++PTPases). We show that ICA 512 is an intrinsic membrane protein of secretory granules expressed in insulin‐producing pancreatic beta‐cells as well as in virtually all other peptide‐secreting endocrine cells and neurons containing neurosecretory granules. ICA 512 is cleaved at its luminal domain and, following exposure at the cell surface, recycles to the Golgi complex region and is sorted into newly formed secretory granules. By immunoprecipitation, anti‐ICA 512 autoantibodies were detected in 15/17 (88%) newly diagnosed IDDM patients, but not in 10/10 healthy subjects. These results suggest that tyrosine phosphorylation participates in some aspect of secretory granule function common to all neuroendocrine cells and that a subset of autoantibodies in IDDM is directed against an integral membrane protein of insulin‐containing granules.