Abstract
Purpose. CP49 is a fiber cell-specific type I cytokeratin, but its function as part of the fiber cell-beaded filament remains unknown. To provide a rational basis for mutational studies that would contribute to an elucidation of function, the study was designed to define elements of CP49s that are highly conserved, discriminate conserved features from species-specific variations, and identify where CP49s have diverged from consensus type I features in their adaptation to selective pressures in the lens. Methods. The primary sequence and gene structure of CP49 from a third vertebrate order was determined from a combination of cDNA and genomic sequencing. Protein product was characterized by SDS-PAGE and Western blot analysis. Consensus features and phylogenetic relationships were identified by multiple alignment. Coiled-coil analysis was conducted to define central rod domains. Results. Trout CP49 is unique among CP49s in having a 39-amino-acid tail domain and shows both unique sequence and allelic variation at the LNDR motif. Comparison of consensus sequences identified unprecedented divergence between CP49s and other type I cytokeratins, including a shortened central rod domain that is conserved among CP49s, but distinct from type I cytokeratins. Conclusions. The considerable differences that have emerged between the consensus features of the type I cytokeratins and the CP49s suggest that the beaded filament serves a significantly different function from intermediate filaments in other epithelia and that type I cytokeratins may have limited utility as a model for studies on lens beaded filaments. These differences, in concert with consensus features identified among CP49s, suggest sites that are probably critical to CP49 function in the lens fiber cell.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 225-235 |
| Number of pages | 11 |
| Journal | Investigative Ophthalmology and Visual Science |
| Volume | 43 |
| Issue number | 1 |
| State | Published - 2002 |
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ASJC Scopus subject areas
- Ophthalmology
Cite this
Unexpected variation in unique features of the lens-specific type I cytokeratin CP49. / Binkley, P. A.; Hess, J.; Casselman, J.; FitzGerald, Paul G.
In: Investigative Ophthalmology and Visual Science, Vol. 43, No. 1, 2002, p. 225-235.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Unexpected variation in unique features of the lens-specific type I cytokeratin CP49
AU - Binkley, P. A.
AU - Hess, J.
AU - Casselman, J.
AU - FitzGerald, Paul G
PY - 2002
Y1 - 2002
N2 - Purpose. CP49 is a fiber cell-specific type I cytokeratin, but its function as part of the fiber cell-beaded filament remains unknown. To provide a rational basis for mutational studies that would contribute to an elucidation of function, the study was designed to define elements of CP49s that are highly conserved, discriminate conserved features from species-specific variations, and identify where CP49s have diverged from consensus type I features in their adaptation to selective pressures in the lens. Methods. The primary sequence and gene structure of CP49 from a third vertebrate order was determined from a combination of cDNA and genomic sequencing. Protein product was characterized by SDS-PAGE and Western blot analysis. Consensus features and phylogenetic relationships were identified by multiple alignment. Coiled-coil analysis was conducted to define central rod domains. Results. Trout CP49 is unique among CP49s in having a 39-amino-acid tail domain and shows both unique sequence and allelic variation at the LNDR motif. Comparison of consensus sequences identified unprecedented divergence between CP49s and other type I cytokeratins, including a shortened central rod domain that is conserved among CP49s, but distinct from type I cytokeratins. Conclusions. The considerable differences that have emerged between the consensus features of the type I cytokeratins and the CP49s suggest that the beaded filament serves a significantly different function from intermediate filaments in other epithelia and that type I cytokeratins may have limited utility as a model for studies on lens beaded filaments. These differences, in concert with consensus features identified among CP49s, suggest sites that are probably critical to CP49 function in the lens fiber cell.
AB - Purpose. CP49 is a fiber cell-specific type I cytokeratin, but its function as part of the fiber cell-beaded filament remains unknown. To provide a rational basis for mutational studies that would contribute to an elucidation of function, the study was designed to define elements of CP49s that are highly conserved, discriminate conserved features from species-specific variations, and identify where CP49s have diverged from consensus type I features in their adaptation to selective pressures in the lens. Methods. The primary sequence and gene structure of CP49 from a third vertebrate order was determined from a combination of cDNA and genomic sequencing. Protein product was characterized by SDS-PAGE and Western blot analysis. Consensus features and phylogenetic relationships were identified by multiple alignment. Coiled-coil analysis was conducted to define central rod domains. Results. Trout CP49 is unique among CP49s in having a 39-amino-acid tail domain and shows both unique sequence and allelic variation at the LNDR motif. Comparison of consensus sequences identified unprecedented divergence between CP49s and other type I cytokeratins, including a shortened central rod domain that is conserved among CP49s, but distinct from type I cytokeratins. Conclusions. The considerable differences that have emerged between the consensus features of the type I cytokeratins and the CP49s suggest that the beaded filament serves a significantly different function from intermediate filaments in other epithelia and that type I cytokeratins may have limited utility as a model for studies on lens beaded filaments. These differences, in concert with consensus features identified among CP49s, suggest sites that are probably critical to CP49 function in the lens fiber cell.
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M3 - Article
C2 - 11773035
AN - SCOPUS:0036139632
VL - 43
SP - 225
EP - 235
JO - Investigative Ophthalmology and Visual Science
JF - Investigative Ophthalmology and Visual Science
SN - 0146-0404
IS - 1
ER -