RGD Reference Report - Mutation in the βA3/A1-crystallin gene impairs phagosome degradation in the retinal pigmented epithelium of the rat. - Rat Genome Database

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Mutation in the βA3/A1-crystallin gene impairs phagosome degradation in the retinal pigmented epithelium of the rat.

Authors: Zigler, J Samuel  Zhang, Cheng  Grebe, Rhonda  Sehrawat, Gitanjali  Hackler, Laszlo  Adhya, Souvonik  Hose, Stacey  McLeod, D Scott  Bhutto, Imran  Barbour, Walid  Parthasarathy, Geetha  Zack, Donald J  Sergeev, Yuri  Lutty, Gerard A  Handa, James T  Sinha, Debasish 
Citation: Zigler JS, etal., J Cell Sci. 2011 Feb 15;124(Pt 4):523-31. doi: 10.1242/jcs.078790. Epub 2011 Jan 25.
RGD ID: 126925759
Pubmed: PMID:21266465   (View Abstract at PubMed)
PMCID: PMC3031366   (View Article at PubMed Central)
DOI: DOI:10.1242/jcs.078790   (Journal Full-text)

Phagocytosis of the shed outer segment discs of photoreceptors is a major function of the retinal pigmented epithelium (RPE). We demonstrate for the first time that βA3/A1-crystallin, a major structural protein of the ocular lens, is expressed in RPE cells. Further, by utilizing the Nuc1 rat, in which the βA3/A1-crystallin gene is mutated, we show that this protein is required by RPE cells for proper degradation of outer segment discs that have been internalized in phagosomes. We also demonstrate that in wild-type RPE, βA3/A1-crystallin is localized to the lysosomes. However, in the Nuc1 RPE, βA3/A1-crystallin fails to translocate to the lysosomes, perhaps because misfolding of the mutant protein masks sorting signals required for proper trafficking. The digestion of phagocytized outer segments requires a high level of lysosomal enzyme activity, and cathepsin D, the major enzyme responsible for proteolysis of the outer segments, is decreased in mutant RPE cells. Interestingly, our results also indicate a defect in the autophagy process in the Nuc1 RPE, which is probably also linked to impaired lysosomal function, because phagocytosis and autophagy might share common mechanisms in degradation of their targets. βA3/A1-crystallin is a novel lysosomal protein in RPE, essential for degradation of phagocytosed material.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
CRYBA1HumanReticular Dystrophy of Retinal Pigment Epithelium  ISOCryba1 (Rattus norvegicus)mRNA:increased expression:retinal pigmented epithelium (rat)RGD 
Cryba1RatReticular Dystrophy of Retinal Pigment Epithelium  IMP mRNA:increased expression:retinal pigmented epithelium (rat)RGD 
Cryba1MouseReticular Dystrophy of Retinal Pigment Epithelium  ISOCryba1 (Rattus norvegicus)mRNA:increased expression:retinal pigmented epithelium (rat)RGD 
Cryba1Nuc1DbsaRatReticular Dystrophy of Retinal Pigment Epithelium  IMP  RGD 
SD-Cryba1Nuc1DbsaRatReticular Dystrophy of Retinal Pigment Epithelium  IMP  RGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Cryba1Ratphagocytosis  IMP  RGD 
Cryba1Ratregulation of autophagy  IMP  RGD 

Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Cryba1Ratabnormal autophagy  IMP  RGD 
Cryba1Nuc1DbsaRatabnormal autophagy  IMP  RGD 
SD-Cryba1Nuc1DbsaRatabnormal autophagy  IMP  RGD 
Cryba1Ratlipofuscinosis  IMP  RGD 
Cryba1Nuc1DbsaRatlipofuscinosis  IMP  RGD 
SD-Cryba1Nuc1DbsaRatlipofuscinosis  IMP  RGD 
Objects Annotated

Genes (Rattus norvegicus)
Cryba1  (crystallin, beta A1)
Cryba1Nuc1Dbsa  (crystallin, beta A1;Nuc1 mutant, Dbsa)

Genes (Mus musculus)
Cryba1  (crystallin, beta A1)

Genes (Homo sapiens)
CRYBA1  (crystallin beta A1)

Strains
SD-Cryba1Nuc1Dbsa  (NA)


Additional Information