Journal
ENEURO
Volume 7, Issue 3, Pages -Publisher
SOC NEUROSCIENCE
DOI: 10.1523/ENEURO.0507-19.2020
Keywords
blindness; extracellular vesicles; phagocytosis; retinitis pigmentosa; rhodopsin; RPE cells
Categories
Funding
- National Institutes of Health [R01-EY-028884, R21-EY-027292, P30-EY-011373, T32-EY-007157]
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Rhodopsin is mislocalized to the inner segment plasma membrane (IS PM) in various blinding disorders including autosomal-dominant retinitis pigmentosa caused by class I rhodopsin mutations. In these disorders, rhodopsin-laden microvesicles are secreted into the extracellular milieu by afflicted photoreceptor cells. Using a Xenopus laevis model expressing class I mutant rhodopsin or Na+/K+-ATPase (NKA) fused to Dendra2, we fluorescently labeled the microvesicles and found retinal pigment epithelial (RPE) cells are capable of engulfing microvesicles containing rhodopsin. A unique sorting mechanism allows class I mutant rhodopsin, but not NKA, to be packaged into the microvesicles. Under normal physiological conditions, NKA is not shed as microvesicles to the extracellular space, but is degraded intracellularly. Those studies provide novel insights into protein homeostasis in the photoreceptor IS PM.
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