Insights into the beaded filament of the eye lens.
Filensin (BFSP1) and CP49 (BFSP2) represent two members of the IF protein superfamily that are thus far exclusively expressed in the eye lens. Mutations in both proteins cause lens cataract and careful consideration of the detail of these cataract phenotypes alerts us to several interesting features concerning the function of filensin (BFSP1) and CP49 (BFSP2) in the lens. With the first filensin (BFSP1) mutation now having been reported to cause a recessive cataract phenotype, there is the suggestion that the mutation could predispose heterozygote carriers to the early onset of age-related nuclear cataract. In the case of CP49 (BFSP2), there are now three unrelated families who have been identified with a common E233 Delta mutation. Very interestingly this is linked to myopia in one family. Despite the apparent phenotypic differences of the filensin (BFSP1) and CP49 (BFSP2) mutations, the data are still consistent with the beaded filament proteins being essential for lens function and specifically contributing to the optical properties of the lens. The fact that none of the mutations thus far reported affect either the conserved LNDR or TYRKLLEGE motifs that flank the central rod domain supports the view that this pair of IF proteins have unusual structural features and a distinctive assembly mechanism. The multiple sequence divergences suggest these proteins have been adapted to the specific functional requirements of lens fibre cells, a function that can be traced from squid to man.
Perng
Ming-Der
MD
School of Biological and Biomedical Sciences, The University of Durham, DH1 3LE, UK. m.d.perng@durham.ac.uk
Zhang
Qingjiong
Q
Quinlan
Roy A
RA
D000818:Animals; D002386:Cataract / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D004847:Epithelial Cells / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D005136:Eye Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D007381:Intermediate Filament Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D007382:Intermediate Filaments / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D007908:Lens, Crystalline / Q000378:metabolism* / Q000503:physiopathology / Q000648:ultrastructure; D009154:Mutation / Q000235:genetics; D017434:Protein Structure, Tertiary / Q000502:physiology
D005136:Eye Proteins; D007381:Intermediate Filament Proteins; C079098:filensin; C084808:phakinin