title: Degradation of nuclear DNA by DNase II-like acid DNase in cortical fiber cells of mouse eye lens.
abstract: The eye lens is composed of fiber cells that differentiate from epithelial cells on its anterior surface. In concert with this differentiation, a set of proteins essential for lens function is synthesized, and the cellular organelles are degraded. DNase II-like acid DNase, also called DNase IIbeta, is specifically expressed in the lens, and degrades the DNA in the lens fiber cells. Here we report that DNase II-like acid DNase is synthesized as a precursor with a signal sequence, and is localized to lysosomes. DNase II-like acid DNase mRNA was found in cortical fiber cells but not epithelial cells, indicating that its expression is induced during the differentiation of epithelial cells into fiber cells. Immunohistochemical and immunocytochemical analyses indicated that DNase II-like acid DNase was colocalized with Lamp-1 in the lysosomes of fiber cells in a relatively narrow region bordering the organelle-free zone, and was often found in degenerating nuclei. A comparison by microarray analysis of the gene expression profiles between epithelial and cortical fiber cells of young mouse lens indicated that some genes for lysosomal enzymes (cathepsins and lipases) were strongly expressed in the fiber cells. These results suggest that the lysosomal system plays a role in the degradation of cellular organelles during lens cell differentiation.
authors.affiliation: Department of Genetics, Osaka University Medical School, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Nakahara
authors.forename: Akiomi
authors.initials: A
authors.lastname: Nagasaka
authors.forename: Masato
authors.initials: M
authors.lastname: Koike
authors.forename: Kaori
authors.initials: K
authors.lastname: Uchida
authors.forename: Kohki
authors.initials: K
authors.lastname: Kawane
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Uchiyama
authors.forename: Shigekazu
authors.initials: S
authors.lastname: Nagata
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002403:Cathepsins / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D004247:DNA / Q000378:metabolism*; D004706:Endodeoxyribonucleases / Q000235:genetics / Q000378:metabolism*; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D007904:Lens Cortex, Crystalline / Q000166:cytology / Q000378:metabolism*; D008049:Lipase / Q000378:metabolism; D051907:Lysosomal Membrane Proteins / Q000378:metabolism; D008247:Lysosomes / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D020411:Oligonucleotide Array Sequence Analysis; D021382:Protein Sorting Signals / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D052118:Lysosomal-Associated Membrane Protein 1
chemical_list: D002403:Cathepsins; D004247:DNA; D004706:Endodeoxyribonucleases; D008049:Lipase; D051907:Lysosomal Membrane Proteins; D021382:Protein Sorting Signals; D012333:RNA, Messenger; D011994:Recombinant Proteins; C052255:Lamp1 protein, mouse; D052118:Lysosomal-Associated Membrane Protein 1; C019329:deoxyribonuclease II