Targeted Deletion of the Lens Fiber Cell–Specific Intermediate Filament Protein Filensin

Alizadeh, Azita; Clark, John I.; Seeberger, Teri; Hess, John F.; Blankenship, Tom; Fitzgerald, Paul G.

doi:10.1167/iovs.03-0224

Cited by 91 publications

(105 citation statements)

References 31 publications

Supporting

Mentioning

100

Contrasting

Order By: Relevance

“…When the lens phenotypes of the different mouse knockouts (46,(50)(51)(52) and the clinical descriptions for the six pedigrees (48,49,(53)(54)(55)(56) covering mutations in BFSP1 and BFSP2 (Table 2) are considered, three key messages emerge: first, beaded filaments are essential to the optical properties of the eye lens; second, beaded filaments are critical to lens transparency, and mutations in BFSP1 and BFSP2 can cause cataract; and third, beaded filaments temper the aging of the eye lens. These messages are developed in the next two sections.…”

Section: Role Of Beaded Filaments In the Eye Lens: Cataractcausing Mumentioning

confidence: 99%

“…BFSP1/2 filaments ensure the correct spatial organization of fiber cells in the lens and the optimal plasma membrane profiles of the lens fiber cells (Figure 2), minimizing light scatter and maximizing the optical function of the lens. Removal of Bfsp2 by targeted gene knockout disrupts these aspects of lens tissue organization (50), increasing light scatter, as seen by slit lamp analysis (50,52). The lenses of patients with BFSP2 mutations are also reported to show increased light scatter (49,53,54), but it remains to be formally tested whether the lens fiber cell profiles and their spatial organization are disrupted by the presence of either BFSP2 or vimentin (19) mutations in human lenses.…”

Section: Figurementioning

confidence: 99%

“…It is not known whether the RNA produced by the mutated BFSP1 is transcribed or removed by the nonsense-mediated decay RNA surveillance pathway. If it is removed in this manner, however, this would effectively create a BFSP1 knockout in the human to parallel the mouse BFSP1 knockout (74). Indeed, in both cases, the lens phenotype is progressive: light scatter increases with age in the mouse, as does cataract in the human.…”

Section: Figurementioning

confidence: 99%

“…The progressive nature of the increased light scatter and cataract development for the mouse Bfsp1 and Bfsp2 knockouts (52,74) and the human cataracts caused by BFSP1 (56) and BFSP2 (49,53,54) mutations suggest that there is an aging element to the beaded filament contribution to the optical properties of the lens. BFSP1 is proteolytically processed differently in lens fiber cells at the center compared with those at the periphery (21), and the lens cytoskeleton, including beaded filament proteins, is often targeted by proteolysis during cataract formation (75,76).…”

Section: The Aging Lens: Accelerated By Mutations In Beaded Filament mentioning

confidence: 99%

See 3 more Smart Citations

Functions of the intermediate filament cytoskeleton in the eye lens

Song¹,

Landsbury²,

Dahm³

et al. 2009

J. Clin. Invest.

160

107

View full text Add to dashboard Cite

Intermediate filaments (IFs) are a key component of the cytoskeleton in virtually all vertebrate cells, including those of the lens of the eye. IFs help integrate individual cells into their respective tissues. This Review focuses on the lens-specific IF proteins beaded filament structural proteins 1 and 2 (BFSP1 and BFSP2) and their role in lens physiology and disease. Evidence generated in studies in both mice and humans suggests a critical role for these proteins and their filamentous polymers in establishing the optical properties of the eye lens and in maintaining its transparency. For instance, mutations in both BFSP1 and BFSP2 cause cataract in humans. We also explore the potential role of BFSP1 and BFSP2 in aging processes in the lens.

show abstract

Section: Role Of Beaded Filaments In the Eye Lens: Cataractcausing Mumentioning

confidence: 99%

Section: Figurementioning

confidence: 99%

Section: Figurementioning

confidence: 99%

Section: The Aging Lens: Accelerated By Mutations In Beaded Filament mentioning

confidence: 99%

See 2 more Smart Citations

Functions of the intermediate filament cytoskeleton in the eye lens

Song¹,

Landsbury²,

Dahm³

et al. 2009

J. Clin. Invest.

160

107

View full text Add to dashboard Cite

show abstract

“…The cells can be upwards of 10 mm long in a mature lens and maintain their shape via an extensive cytoskeleton (Perng et al 2007). The cytoskeletal structure of these cells is vital for transparency, as lenses lacking key filament proteins are opaque despite the fibre cells maintaining typical morphology (Alizadeh et al 2002). In order to act as an effective optical focusing device, the lens must maintain several unique properties.…”

Section: Lens Structure and Ageingmentioning

confidence: 99%

Biophysical chemistry of the ageing eye lens

Ray

2015

Biophys Rev

View full text Add to dashboard Cite

This review examines both recent and historical literature related to the biophysical chemistry of the proteins in the ageing eye, with a particular focus on cataract development. The lens is a vital component of the eye, acting as an optical focusing device to form clear images on the retina. The lens maintains the necessary high transparency and refractive index by expressing crystallin proteins in high concentration and eliminating all large cellular structures that may cause light scattering. This has the consequence of eliminating lens fibre cell metabolism and results in mature lens fibre cells having no mechanism for protein expression and a complete absence of protein recycling or turnover. As a result, the crystallins are some of the oldest proteins in the human body. Lack of protein repair or recycling means the lens tends to accumulate damage with age in the form of protein posttranslational modifications. The crystallins can be subject to a wide range of age-related changes, including isomerisation, deamidation and racemisation. Many of these modification are highly correlated with cataract formation and represent a biochemical mechanism for age-related blindness.

show abstract

Effects of truncations in the N‐ and C‐terminal domains of filensin on filament formation with phakinin in cell‐free conditions and cultured cells

Tashiro,

Nakamura,

Kuratani

et al. 2023

FEBS Open Bio

View full text Add to dashboard Cite

Filensin and phakinin are lens fiber cell‐specific proteins that constitute the beaded filaments that are critical for maintaining lens transparency. In the Shumiya cataract rat, filensin 94 kDa undergoes N‐ and C‐terminal proteolytic processing to give a transient 50 kDa fragment and a final 38 kDa fragment, just before opacification. To characterize effects of this processing on filensin function, recombinant proteins representing the two filensin fragments, termed Fil(30‐416) and Fil(30‐369), respectively, were examined. Fil(30‐416) lacks the N‐terminal 29 amino acids and the C‐terminal 248 amino acids. Fil(30‐369) lacks the N‐terminal 29 residues and the C‐terminal 295 residues. In cell‐free assembly characterized by electron microscopy, filensin and Fil(30‐416) co‐polymerized with phakinin and formed rugged, entangled filaments, whereas Fil(30‐369) formed only aggregates. In cultured SW‐13 and MCF‐7 cells expressing fluorescent fusion proteins, filensin and Fil(30‐416) co‐polymerized with phakinin and formed cytoplasmic sinuous filaments with different widths, while Fil(30‐369) gave aggregates. Therefore, while truncation of the N‐terminal 29 amino acids did not affect filament formation, truncation of the C‐terminal 295 but not the 248 residues resulted in failure of filament formation. These results indicate that the tail B region (residues 370–416) of rat filensin is essential for filament formation with phakinin. Truncation of the tail B region by proteolytic processing in the cataract rat lens might interfere with beaded filament formation and thereby contribute to opacification.

show abstract

Targeted Deletion of the Lens Fiber Cell–Specific Intermediate Filament Protein Filensin

Cited by 91 publications

References 31 publications

Functions of the intermediate filament cytoskeleton in the eye lens

Functions of the intermediate filament cytoskeleton in the eye lens

Biophysical chemistry of the ageing eye lens

Effects of truncations in the N‐ and C‐terminal domains of filensin on filament formation with phakinin in cell‐free conditions and cultured cells

Contact Info

Product

Resources

About