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Abstract #25369 Published in IGR 12-1
Glutamate induces cell surface translocation of annexin A2 in retinal ganglion cells
Valapala M; Borejdo J; Vishwanatha J KFASEB Journal 2009; 23: S1
Glutamate-induced elevation in intracellular Ca(2+) has been implicated in the loss of retinal ganglion cells (RGCs) in glaucoma. RGCs respond to excitotoxic injury by activating an extracellular proteolytic cascade involving the components of the plasmin-plasminogen system. Annexin A2 is a Ca(2+) dependent phospholipid binding protein and serves as an extracellular proteolytic center by recruiting tissue plasminogen activator (tPA) and plasminogen and mediating localized generation of plasmin. Here we characterize the expression of annexin A2 in the rat RGCs. Ca(2+) imaging and time lapse microscopy demonstrated glutamate-induced Ca(2+) influx. We showed that glutamate mobilized both endogenous and GFP fused annexin A2 to the cell surface in a process dependent on the NMDA receptor activity. By in vitro plasmin generation assay we demonstrated that annexin A2 forms a catalytically active plasmin generating complex on glutamate treatment and this activity is inhibited by blocking the N-terminus of annexin A2. Phosphorylation of Y23 at the N-terminus by Src kinase is critical and mutation of Y23 to Y23F inhibits the translocation process. Mutations in the p11 binding site also inhibited annexin A2 cell surface translocation. A hexapeptide against the N-terminal tPA binding site inhibited annexin A2-mediated plasmin generation. These results suggest an involvement of annexin A2 in neuronal cell death processes.
M. Valapala. Biomedical Sciences, .
Classification:
2.13 Retina and retinal nerve fibre layer (Part of: 2 Anatomical structures in glaucoma)
11.8 Neuroprotection (Part of: 11 Medical treatment)