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ARS Home » Northeast Area » Boston, Massachusetts » Jean Mayer Human Nutrition Research Center On Aging » Research » Publications at this Location » Publication #146837
Title: GAS6 BINDING TO PHOTORECEPTOR OUTER SEGMENTS REQUIRES GAMMA-CARBOXYGLUTAMIC ACID (GLA) AND CA2+ AND IS REQUIRED FOR OS PHAGOCYTOSIS BY RPE CELLS IN VITRO

Author
item HALL, M - JULES STEIN EYE INST
item OBIN, MARTIN - HNRCA
item PRIETO, A - INDIANA U
item BURGESS, B - JULES STEIN EYE INST
item ABRAMS, T - JULES STEIN EYE INST

Submitted to: Experimental Eye Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/23/2002
Publication Date: 8/1/2002
Citation: HALL, M.O., OBIN, M.S., PRIETO, A.L., BURGESS, B.L., ABRAMS, T.A. GAS6 BINDING TO PHOTORECEPTOR OUTER SEGMENTS REQUIRES GAMMA-CARBOXYGLUTAMIC ACID (GLA) AND CA2+ AND IS REQUIRED FOR OS PHAGOCYTOSIS BY RPE CELLS IN VITRO. EXPERIMENTAL EYE RESEARCH. 75:391-400,2002.

Interpretive Summary: Mutations in a receptor for growth arrest specific gene (Gas)6, cause retinal degeneration and blindness in humans and animals. This degeneration results from an inability of the retinal epithelium to ingest and digest worn tips of the photoreceptors (rods and cones). This study demonstrates for the first time that the function of Gas6 in the retina requires that it be modified by a vitamin K-dependent reaction. When expressed in the presence of a vitamin K antagonist (warfarin), Gas6 fails to interact with its receptor on the retinal epithelium and fails to stimulate ingestion of photoreceptor tips. These data provide the first evidence of and mechanism for the role for vitamin K in preserving visual function.

Technical Abstract: The phagocytosis of photoreceptor outer segments by retinal pigment epithelial (RPE) cells plays a critical role in preserving normal retinal function. We have performed a series of experiments to further dissect the interactions of Gas6 with the OS and RPE and to determine the specific calcium requirements necessary for Gas6 to exert its stimulatory effect on phagocytosis.These experiments show that Gas6 must bind to OS before the stimulation of OS ingestion can occur and that this binding requires a Ca2+ concentration of 500 micromolar . The same Ca2+ concentration is required for the Gas6 mediated stimulation of OS ingestion. We further demonstrate that in order to bind to OS and to stimulate OS phagocytosis, Gas6 requires -carboxylation in a vitamin K-dependent reaction. These studies further underscore the importance of Gas6 in the phagocytic function of the RPE and open new avenues of investigation to understand the molecular events mediated and triggered by Gas6, and its interaction with the OS and RPE.