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Modulation of phospholipid metabolism by annexins

Reference	BB/D018099/1
Principal Investigator / Supervisor	Professor Stephen Moss
Co-Investigators / Co-Supervisors	Dr Timothy Levine
Institution	University College London
Department	Institute of Ophthalmology
Funding type	Research
Value (£)	363,954
Status	Completed
Type	Research Grant
Start date	01/09/2006
End date	31/08/2009
Duration	36 months

Abstract

Annexin 6 is an abundant protein that binds to negatively-charged phospholipids in the presence of calcium. In mice lacking annexin 6 generated in our lab, we have observed a number of phenotype including the presence of microparticles in the blood, reduced phosphatidylserine in mitochondrial membranes, failure to deposit adipose tissue, that all suggest defective phospholipid metabolism and trafficking. Here, we will use adipocytes and hepatocytes from control and null mutant mice to investigate lipid trafficking and metabolism. Our approach will employ lipid purification and mass spec analysis, biochemistry, live cell imaging and analysis of mitochondrial function. This is a comprehensive programme of work that will provide new insight into annexin function, and in particular the role of annexin 6 in the regulation of phospholipid metabolism.

Summary

Phospholipids are essential components of the human diet yet their excessive consumption, particularly in western societies is associated with obesity, diabetes and cardiovascular disease. Phospholipids are essential because they form the membranes that not only encapsulate all cells, they also form the membranes inside cells that partition cellular constituents into organelles. There are many different types of phospholipid, and these can serve both structural and signaling functions. We have observed abnormalities in a mutant mouse strain that lacks annexin 6, one of a large and abundant family of proteins that binds to phospholipids, that is strongly suggestive of defective phospholipid metabolism. The proposed research will use cells from these mice to investigate the expression and movement of certain phospholipids within these cells, and to understand how annexin 6 is involved in these activities.

Committee	Closed Committee - Biochemistry & Cell Biology (BCB)
Research Topics	X – not assigned to a current Research Topic
Research Priority	X – Research Priority information not available
Research Initiative	X - not in an Initiative
Funding Scheme	X – not Funded via a specific Funding Scheme

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