Signal integration by annexin 2 during retinal phagocytosis. (360G-Wellcome-090669_Z_09_Z)

£290,342

Our previous WT-funded work has shown that annexin 2 is required for the prompt circadian activation of Src and FAK in retinal pigment epithelial cells, that is in turn required for the phagocytosis of shed photoreceptor outer segments. Annexin 2 is regulated by phosphoinositides, calcium and tyrosine phosphorylation, but it is not known how these second messengers and tyrosine phosphorylation combine to regulate annexin 2 function and thus retinal phagocytosis. Our key goals are to i) exami ne annexin 2 tyrosine phosphorylation during retinal phagocytosis in the broader context of total cellular tyrosine kinase activation, ii) specifically investigate the spatial and temporal relationship between annexin 2, Src, FAK and Mer during phagocytosis, iii) use annexin 2 mutants in cell culture and in vivo (in AAV vectors) to determine how second messengers and tyrosine phosphorylation combine to regulate annexin 2, and iv) evaluate the effects of expression of these mutants on retinal and visual function. The work will be conducted in control and annexin 2 KO mice, and in cultured cells using live cell imaging. In addition we will use existing rodent strains to examine annexin 2 in RPE cells lacking FAK and Mer.

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Grant Details

Amount Awarded 290342
Applicant Surname Moss
Approval Committee Molecules, Genes and Cells Funding Committee
Award Date 2010-02-04T00:00:00+00:00
Financial Year 2009/10
Grant Programme: Title Project Grant
Internal ID 090669/Z/09/Z
Lead Applicant Prof Stephen Moss
Partnership Value 290342
Planned Dates: End Date 2014-02-28T00:00:00+00:00
Planned Dates: Start Date 2010-09-01T00:00:00+00:00
Recipient Org: Country United Kingdom
Region Greater London