Laboratory of Molecular Biology

About: Laboratory of Molecular Biology is a facility organization based out in Cambridge, Cambridgeshire, United Kingdom. It is known for research contribution in the topics: Gene & RNA. The organization has 19395 authors who have published 24236 publications receiving 2101480 citations.

Serum amyloid P component controls chromatin degradation and prevents antinuclear autoimmunity.

Abstract: Serum amyloid P component (SAP), a highly conserved plasma protein named for its universal presence in amyloid deposits1, is the single normal circulating protein that shows specific calcium-dependent binding to DNA and chromatin in physiological conditions2,3. The avid binding of SAP displaces H1-type histones and thereby solubilizes native long chromatin, which is otherwise profoundly insoluble at the physiological ionic strength of extracellular fluids4. Furthermore, SAP binds in vivo both to apoptotic cells5, the surface blebs of which bear chromatin fragments6, and to nuclear debris released by necrosis7. SAP may therefore participate in handling of chromatin exposed by cell death2,3,4,7. Here we show that mice with targeted deletion of the SAP gene8 spontaneously develop antinuclear autoimmunity and severe glomerulonephritis, a phenotype resembling human systemic lupus erythematosus, a serious autoimmune disease. The SAP–/– mice also have enhanced anti-DNA responses to immunization with extrinsic chromatin, and we demonstrate that degradation of long chromatin is retarded in the presence of SAP both in vitro and in vivo. These findings indicate that SAP has an important physiological role, inhibiting the formation of pathogenic autoantibodies against chromatin and DNA, probably by binding to chromatin and regulating its degradation.

Transglutaminase is essential in receptor-mediated endocytosis of alpha 2-macroglobulin and polypeptide hormones.

Abstract: The receptor-mediated endocytosis of alpha 2-macroglobulin can be inhibited by a diverse group of chemical compounds all of which share the property of being inhibitors of one form of cellular transglutaminase. The present results strongly suggest that protein cross-linking may be essential for receptor-mediated endocytosis of some protein and polypeptide hormones.