Bicarbonate-dependent secretion and proteolytic processing of recombinant myocilin.
Myocilin is an extracellular glycoprotein of poorly understood function. Mutations of this protein are involved in glaucoma, an optic neuropathy characterized by a progressive and irreversible visual loss and frequently associated with elevated intraocular pressure. We previously showed that recombi...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3547000?pdf=render |
| _version_ | 1818195123212648448 |
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| author | José-Daniel Aroca-Aguilar Francisco Martínez-Redondo Alba Martín-Gil Jesús Pintor Miguel Coca-Prados Julio Escribano |
| author_facet | José-Daniel Aroca-Aguilar Francisco Martínez-Redondo Alba Martín-Gil Jesús Pintor Miguel Coca-Prados Julio Escribano |
| author_sort | José-Daniel Aroca-Aguilar |
| collection | DOAJ |
| description | Myocilin is an extracellular glycoprotein of poorly understood function. Mutations of this protein are involved in glaucoma, an optic neuropathy characterized by a progressive and irreversible visual loss and frequently associated with elevated intraocular pressure. We previously showed that recombinant myocilin undergoes an intracellular proteolytic processing by calpain II which cleaves the central region of the protein, releasing one N- and one C-terminal fragment. Myocilin cleavage is reduced by glaucoma mutations and it has been proposed to participate in intraocular pressure modulation. To identify possible factors regulating the proteolytic processing of recombinant myocilin, we used a cellular model in which we analyzed how different culture medium parameters (i.e., culture time, cell density, pH, bicarbonate concentration, etc.) affect the presence of the extracellular C-terminal fragment. Extracellular bicarbonate depletion associated with culture medium acidification produced a reversible intracellular accumulation of full-length recombinant myocilin and incremented its intracellular proteolytic processing, raising the extracellular C-terminal fragment percentage. It was also determined that myocilin intracellular accumulation depends on its N-terminal region. These data suggest that aqueous humor bicarbonate variations could also modulate the secretion and cleavage of myocilin present in ocular tissues. |
| first_indexed | 2024-12-12T01:13:11Z |
| format | Article |
| id | doaj.art-0c43ec340af441879fd8b3aead11c7fb |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-12T01:13:11Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-0c43ec340af441879fd8b3aead11c7fb2022-12-22T00:43:25ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0181e5438510.1371/journal.pone.0054385Bicarbonate-dependent secretion and proteolytic processing of recombinant myocilin.José-Daniel Aroca-AguilarFrancisco Martínez-RedondoAlba Martín-GilJesús PintorMiguel Coca-PradosJulio EscribanoMyocilin is an extracellular glycoprotein of poorly understood function. Mutations of this protein are involved in glaucoma, an optic neuropathy characterized by a progressive and irreversible visual loss and frequently associated with elevated intraocular pressure. We previously showed that recombinant myocilin undergoes an intracellular proteolytic processing by calpain II which cleaves the central region of the protein, releasing one N- and one C-terminal fragment. Myocilin cleavage is reduced by glaucoma mutations and it has been proposed to participate in intraocular pressure modulation. To identify possible factors regulating the proteolytic processing of recombinant myocilin, we used a cellular model in which we analyzed how different culture medium parameters (i.e., culture time, cell density, pH, bicarbonate concentration, etc.) affect the presence of the extracellular C-terminal fragment. Extracellular bicarbonate depletion associated with culture medium acidification produced a reversible intracellular accumulation of full-length recombinant myocilin and incremented its intracellular proteolytic processing, raising the extracellular C-terminal fragment percentage. It was also determined that myocilin intracellular accumulation depends on its N-terminal region. These data suggest that aqueous humor bicarbonate variations could also modulate the secretion and cleavage of myocilin present in ocular tissues.http://europepmc.org/articles/PMC3547000?pdf=render |
| spellingShingle | José-Daniel Aroca-Aguilar Francisco Martínez-Redondo Alba Martín-Gil Jesús Pintor Miguel Coca-Prados Julio Escribano Bicarbonate-dependent secretion and proteolytic processing of recombinant myocilin. PLoS ONE |
| title | Bicarbonate-dependent secretion and proteolytic processing of recombinant myocilin. |
| title_full | Bicarbonate-dependent secretion and proteolytic processing of recombinant myocilin. |
| title_fullStr | Bicarbonate-dependent secretion and proteolytic processing of recombinant myocilin. |
| title_full_unstemmed | Bicarbonate-dependent secretion and proteolytic processing of recombinant myocilin. |
| title_short | Bicarbonate-dependent secretion and proteolytic processing of recombinant myocilin. |
| title_sort | bicarbonate dependent secretion and proteolytic processing of recombinant myocilin |
| url | http://europepmc.org/articles/PMC3547000?pdf=render |
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