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• W1448702246 abstract "Photoreceptor outer segments (OS) in the vertebrate retina undergo a process of continual renewal involving shedding of disc membranes that are cleared by phagocytic uptake into the retinal pigment epithelium (RPE). In dystrophic Royal College of Surgeons (RCS) rats, OS phagocytosis is blocked by a mutation in the gene encoding the receptor tyrosine kinase MERTK. To identify proteins tyrosine-phosphorylated downstream of MERTK in the RPE, MALDI-mass spectrometry with peptide-mass fingerprinting was used in comparative studies of RCS congenic and dystrophic rats. At times corresponding to peak phagocytic activity, the RAB GTPase effector GDP dissociation inhibitor alpha (GDI1) was found to undergo tyrosine phosphorylation only in congenic rats. In cryosections of native RPE/choroid, GDI1 colocalized with MERTK and the intracellular tyrosine-kinase SRC. In cultured RPE-J cells, and in transfected heterologous cells, MERTK stimulated SRC-mediated tyrosine phosphorylation of GDI1. In OS-fed RPE-J cells, GDI1 colocalized with MERTK and SRC on apparent phagosomes located near the apical membrane. In addition, both GDI1 and RAB5, a regulator of vesicular transport, colocalized with ingested OS. Taken together, these findings identify a novel role of MERTK signaling in membrane trafficking in the RPE that is likely to subserve mechanisms of phagosome formation." @default.
• W1448702246 created "2016-06-24" @default.
• W1448702246 creator A5001456988 @default.
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• W1448702246 creator A5068393306 @default.
• W1448702246 creator A5073199916 @default.
• W1448702246 date "2015-11-01" @default.
• W1448702246 modified "2023-09-23" @default.
• W1448702246 title "MERTK signaling in the retinal pigment epithelium regulates the tyrosine phosphorylation of GDP dissociation inhibitor alpha from the GDI/CHM family of RAB GTPase effectors" @default.
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• W1448702246 doi "https://doi.org/10.1016/j.exer.2015.08.006" @default.
• W1448702246 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4624558" @default.
• W1448702246 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/26283020" @default.
• W1448702246 hasPublicationYear "2015" @default.
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