ABCF1 extrinsically regulates retinal pigment epithelial cell phagocytosis

Guo, Feiye; Ding, Ying; Caberoy, Nora B.; Alvarado, Gabriela; Wang, Feng; Chen, Rui; Li, Wei

doi:10.1091/mbc.e14-09-1343

Cited by 26 publications

(38 citation statements)

References 37 publications

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“…MBP-Mesd fusion protein and MBP control were expressed in BL21(DE3) bacteria and purified using amylose columns, as described (Guo et al, 2015a). Purified MBP-Mesd and MBP were dialyzed against phosphate-buffered saline (PBS), analyzed for purity by SDS-PAGE and verified by Western blot using affinity-purified anti-Mesd antibody (Thermo Fisher Scientific, Waltham, MA).…”

Section: Methodsmentioning

confidence: 99%

“…Primary RPE cells were prepared, as previously described (Guo et al, 2015a). Briefly, C57BL/6 mice at postnatal day 10 were euthanized by CO 2 inhalation.…”

Section: Methodsmentioning

confidence: 99%

“…After POS detachment in the above experiment, bovine retinas were collected, homogenized in RIPA buffer (Thermo Fisher Scientific, Waltham, MA), and analyzed by Western blot using anti-Mesd antibody or anti-β-actin antibody (Cell Signaling, Danvers, MA) (Guo et al, 2015a). …”

Section: Methodsmentioning

confidence: 99%

“…D407 RPE cells with engulfed pHrodo-labeled POSs in the above phagocytosis assay were fixed with 10% buffered formalin, permeabilized with PBS containing 1% Triton X-100, and incubated with anti-Rab7 antibody (Abcam, Cambridge, MA) (Guo et al, 2015a). After washing, bound antibody was detected using Alexa Fluor 488-labeled secondary antibody.…”

Section: Methodsmentioning

confidence: 99%

“…We recently developed an innovative technology of open reading frame phage display (OPD) for the unbiased identification of phagocytosis ligands in the absence of receptor information (Caberoy and Li, 2012; Caberoy et al, 2010a; Li, 2012). We further combined OPD with next generation DNA sequencing (NGS) as the only technology of “ligandomics” to globally identify cell-wide phagocytosis ligands (Ding et al, 2015; Guo et al, 2015a). One of the identified proteins for microglial phagocytosis is mesoderm development candidate 2 (Mesd or Mesdc2) (unpublished data, Ding et al).…”

Section: Introductionmentioning

confidence: 99%

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Mesd extrinsically promotes phagocytosis by retinal pigment epithelial cells

et al. 2016

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Phagocytosis is a critical process to maintain tissue homeostasis. In the retina, photoreceptor cells renew their photo-excitability by shedding photoreceptor outer segments (POSs) in a diurnal rhythm. Shed POSs are phagocytosed by retinal pigment epithelial (RPE) cells to prevent debris accumulation, retinal degeneration and blindness. Phagocytosis ligands are the key to understanding how RPE recognizes shed POSs. Here we characterized mesoderm development candidate 2 (Mesd or Mesdc2), an endoplasmic reticulum (ER) chaperon for low-density lipoprotein receptor-related proteins (LRPs), to extrinsically promote RPE phagocytosis. The results showed that Mesd stimulated phagocytosis of fluorescence-labeled POS vesicles by D407 RPE cells. Ingested POSs were partially degraded within 3 h in some RPE cells to dispense undegradable fluorophore throughout the cytoplasm. Internalized POSs were colocalized with phagosome biomarker Rab7, suggesting that Mesd-mediated engulfment is involved in a phagocytosis pathway. Mesd also facilitated phagocytosis of POSs by primary RPE cells. Mesd bound to unknown phagocytic receptor(s) on RPE cells. Mesd was detected in the cytoplasm, but not nuclei, of different retinal layers and is predominantly expressed in the ER-free cellular compartment of POSs. Mesd was not secreted into medium from healthy cells but passively released from apoptotic cells with increased membrane permeability. Released Mesd selectively bound to the surface of POS vesicles and apoptotic cells, but not healthy cells. These results suggest that Mesd may be released from and bind to shed POSs to facilitate their phagocytic clearance.

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Section: Methodsmentioning

confidence: 99%

“…Primary RPE cells were prepared, as previously described (Guo et al, 2015a). Briefly, C57BL/6 mice at postnatal day 10 were euthanized by CO 2 inhalation.…”

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Mesd extrinsically promotes phagocytosis by retinal pigment epithelial cells

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ABC‐F translation factors: from antibiotic resistance to immune response

et al. 2020

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Energy-dependent Translational Throttle A (EttA) from E. coli is a paradigmatic ABC-F protein that controls the first step in polypeptide elongation on the ribosome according to the cellular energy status. Biochemical and structural studies have established that ABC-F proteins generally function as translation factors that modulate the conformation of the peptidyl transferase center upon binding to the ribosomal tRNA exit site. These factors, present in both prokaryotes and eukaryotes but not in archaea, use related molecular mechanisms to modulate protein synthesis for heterogenous purposes, ranging from antibiotic resistance and rescue of stalled ribosomes to modulation of the mammalian immune response. Here we review the canonical studies characterizing the phylogeny, regulation, ribosome interactions, and mechanisms of action of the bacterial ABC-F proteins, and discuss the implications of these studies for the molecular function of eukaryotic ABC-F proteins, including the three human family members.

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The human ATP‐binding cassette (ABC) transporter superfamily

2022

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The ATP‐binding cassette (ABC) transporter superfamily comprises membrane proteins that efflux various substrates across extra‐ and intracellular membranes. Mutations in ABC genes cause 21 human disorders or phenotypes with Mendelian inheritance, including cystic fibrosis, adrenoleukodystrophy, retinal degeneration, cholesterol, and bile transport defects. To provide tools to study the function of human ABC transporters we compiled data from multiple genomics databases. We analyzed ABC gene conservation within human populations and across vertebrates and surveyed phenotypes of ABC gene mutations in mice. Most mouse ABC gene disruption mutations have a phenotype that mimics human disease, indicating they are applicable models. Interestingly, several ABCA family genes, whose human function is unknown, have cholesterol level phenotypes in the mouse. Genome‐wide association studies confirm and extend ABC traits and suggest several new functions to investigate. Whole‐exome sequencing of tumors from diverse cancer types demonstrates that mutations in ABC genes are not common in cancer, but specific genes are overexpressed in select tumor types. Finally, an analysis of the frequency of loss‐of‐function mutations demonstrates that many human ABC genes are essential with a low level of variants, while others have a higher level of genetic diversity.

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ABCF1 extrinsically regulates retinal pigment epithelial cell phagocytosis

Cited by 26 publications

References 37 publications

Mesd extrinsically promotes phagocytosis by retinal pigment epithelial cells

Mesd extrinsically promotes phagocytosis by retinal pigment epithelial cells

ABC‐F translation factors: from antibiotic resistance to immune response

The human ATP‐binding cassette (ABC) transporter superfamily

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