Departmental Papers (Dental)

Document Type

Journal Article

Date of this Version

2015

Publication Source

Molecular Neurobiology

Volume

52

Start Page

1135

Last Page

1151

DOI

10.1007/s12035-014-8920-5

Abstract

A main requisite in the phagocytosis of ingested
material is a coordinated series of maturation steps which lead
to the degradation of ingested cargo. Photoreceptor outer
segment (POS) renewal involves phagocytosis of the distal
disk membranes by the retinal pigment epithelium (RPE).
Previously, we identified melanoregulin (MREG) as an intra-
cellular cargo-sorting protein required for the degradation of
POS disks. Here, we provide evidence that MREG-dependent
processing links both autophagic and phagocytic processes in
LC3-associated phagocytosis (LAP). Ingested POS
phagosomes are associated with endogenous LC3 and
MREG. The LC3 association with POSs exhibited properties
of LAP; it was independent of rapamycin pretreatment, but
dependent on Atg5. Loss of MREG resulted in a decrease in
the extent of LC3-POS association. Studies using DQ™-BSA
suggest that loss of MREG does not compromise the associ-
ation and fusion of LC3-positive phagosomes with lysosomes.
Furthermore, the mechanism of MREG action is likely
through a protein complex that includes LC3, as determined
by colocalization and immunoprecipitation in both RPE cells
and macrophages. We posit that MREG participates in
coordinating the association of phagosomes with LC3 for
content degradation with the loss of MREG leading to
phagosome accumulation.

Keywords

Melanoregulin . Autophagy . Retinal pigment epithelium . Phagocytosis . Microtubule-associated protein 1 light chain 3

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Date Posted: 08 December 2022

This document has been peer reviewed.