RGD Reference Report - Mertk drives myosin II redistribution during retinal pigment epithelial phagocytosis. - Rat Genome Database

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Mertk drives myosin II redistribution during retinal pigment epithelial phagocytosis.

Authors: Strick, DJ  Feng, W  Vollrath, D 
Citation: Strick DJ, etal., Invest Ophthalmol Vis Sci. 2009 May;50(5):2427-35. Epub 2008 Dec 30.
RGD ID: 6902913
Pubmed: PMID:19117932   (View Abstract at PubMed)
DOI: DOI:10.1167/iovs.08-3058   (Journal Full-text)

PURPOSE: Mertk is a key phagocytic receptor in the immune, male reproductive, and visual systems. In the retinal pigment epithelium, Mertk is required for the daily ingestion of photoreceptor outer segment (OS) tips. Loss of Mertk function causes retinal degeneration in rats, mice, and humans; however, little is known about the mechanism by which Mertk regulates the ingestion phase of retinal pigment epithelial (RPE) phagocytosis. To address this, the authors sought proteins that associated with Mertk during OS phagocytosis. METHODS: Lysates of RPE-J cells challenged with OS for various times were immunoprecipitated with Mertk antibody. Potential interacting proteins were identified by mass spectrometry and characterized with confocal microscopy, pharmacologic inhibition, and siRNA knockdown coupled with an in vitro phagocytic assay in primary RPE cells. RESULTS: Myh9, the non-muscle myosin II-A heavy chain, was enriched in immunoprecipitates from OS-treated samples. Myosin II-A and II-B isoforms exhibited a striking redistribution in wild-type rat primary RPE cells challenged with OS, moving from the cell periphery to colocalize with ingested OS over time. In contrast, myosin II-A redistribution in response to OS was blunted in primary RPE cells from RCS rats, which lack functional Mertk. Wild-type rat primary RPE cells treated with the myosin II-specific inhibitor blebbistatin or myosin II siRNAs exhibited a significant phagocytic defect. CONCLUSIONS: Mertk mobilizes myosin II from the RPE cell periphery to sites of OS engulfment, where myosin II function is essential for the normal phagocytic ingestion of OS.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
positive regulation of phagocytosis  IMP 6902913 RGD 

Cellular Component
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
lateral plasma membrane  IDA 6902913 RGD 
phagocytic vesicle located_inIDA 6902913 RGD 

Molecular Function
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
protein kinase binding  IPIMertk (Rattus norvegicus)6902913 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Myh9  (myosin, heavy chain 9)


Additional Information