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Research ArticleResearch Article: New Research, Disorders of the Nervous System

RPE Cells Engulf Microvesicles Secreted by Degenerating Rod Photoreceptors

Philip Ropelewski and Yoshikazu Imanishi
eNeuro 6 May 2020, 7 (3) ENEURO.0507-19.2020; DOI: https://doi.org/10.1523/ENEURO.0507-19.2020
Philip Ropelewski
Department of Pharmacology, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106
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Yoshikazu Imanishi
Department of Pharmacology, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106
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Abstract

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.

  • blindness
  • extracellular vesicles
  • phagocytosis
  • retinitis pigmentosa
  • rhodopsin
  • RPE cells

Footnotes

  • The authors declare no competing financial interests.

  • This work was supported by National Institutes of Health Grants R01-EY-028884 (to Y.I.), R21-EY-027292 (to Y.I.), P30-EY-011373 (to Case Western Reserve University), and T32-EY-007157 (to P.R.).

This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license, which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.

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RPE Cells Engulf Microvesicles Secreted by Degenerating Rod Photoreceptors
Philip Ropelewski, Yoshikazu Imanishi
eNeuro 6 May 2020, 7 (3) ENEURO.0507-19.2020; DOI: 10.1523/ENEURO.0507-19.2020

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RPE Cells Engulf Microvesicles Secreted by Degenerating Rod Photoreceptors
Philip Ropelewski, Yoshikazu Imanishi
eNeuro 6 May 2020, 7 (3) ENEURO.0507-19.2020; DOI: 10.1523/ENEURO.0507-19.2020
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Keywords

  • blindness
  • extracellular vesicles
  • phagocytosis
  • retinitis pigmentosa
  • rhodopsin
  • RPE cells

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