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Trafficking of osteonectin by retinal pigment epithelial cells: evidence for basolateral secretion

Trafficking of osteonectin by retinal pigment epithelial cells: evidence for basolateral secretion
Trafficking of osteonectin by retinal pigment epithelial cells: evidence for basolateral secretion

Osteonectin is a glycoprotein that modulates several aspects of cellular behaviour including proliferation and adhesion. The retinal pigment epithelium forms a continuous monolayer of polarised cells immediately bellow the neuroretina, and is integral to the homeostasis of photoreceptor cells. While osteonectin is expressed by normal retinal pigment epithelium in situ, its expression is significantly increased in retinal pigment epithelial cells associated with several common retinal diseases. This pattern of expression implies an important role for osteonectin in the biology of retinal pigment epithelial cells. However, the trafficking, processing, and eventual fate of osteonectin in these cells is not clear at present. Although the theoretical report of a leader sequence within the osteonectin open reading frame and its extracellular presence in some tissues indirectly support secretion of the protein, there is no direct experimental demonstration of the secretion route to date. As a first step towards understanding the role of osteonectin in retinal pigment epithelium, we studied the intracellular distribution and trafficking of the protein in living cells. Here, we present experimental evidence that a precursor osteonectin fusion protein is targeted to the endoplasmic reticulum/Golgi pathway, with a likely basal secretion in retinal pigment epithelial cells. In addition, we show that the precursor osteonectin protein having the leader sequence masked fails to undergo secretion leading to cell death, a phenotype which may be of relevance not only for retinal pathology, but also for other diseases such as the bone disorder known as pseudoachondroplasia that is associated with a lack of osteonectin secretion.

Achondroplasia, Cell Adhesion, Cell Death, Cell Line, Cell Polarity, Cell Proliferation, Golgi Apparatus, Humans, Osteonectin, Photoreceptor Cells, Pigment Epithelium of Eye, Protein Sorting Signals, Protein Transport, Recombinant Fusion Proteins, Journal Article, Research Support, Non-U.S. Gov't
1357-2725
85-92
Ratnayaka, Arjuna
002499b8-1a9f-45b6-9539-5ac145799dfd
Paraoan, Luminita
252bc6c9-e9b1-4bbb-a2d3-d7fb91826b0e
Nelson, Glyn
c3556400-ab7e-452e-81c7-a580f86f9821
Spiller, Dave G
e2d4ae55-26f1-435f-88b7-cded8d3ebc56
White, Michael R H
d0d97c08-20c6-4452-a7f4-db92ae05109c
Hiscott, Paul
c5f18179-36ab-4466-98a3-906e6638e10a
Ratnayaka, Arjuna
002499b8-1a9f-45b6-9539-5ac145799dfd
Paraoan, Luminita
252bc6c9-e9b1-4bbb-a2d3-d7fb91826b0e
Nelson, Glyn
c3556400-ab7e-452e-81c7-a580f86f9821
Spiller, Dave G
e2d4ae55-26f1-435f-88b7-cded8d3ebc56
White, Michael R H
d0d97c08-20c6-4452-a7f4-db92ae05109c
Hiscott, Paul
c5f18179-36ab-4466-98a3-906e6638e10a

Ratnayaka, Arjuna, Paraoan, Luminita, Nelson, Glyn, Spiller, Dave G, White, Michael R H and Hiscott, Paul (2007) Trafficking of osteonectin by retinal pigment epithelial cells: evidence for basolateral secretion. International Journal of Biochemistry & Cell Biology, 39 (1), 85-92. (doi:10.1016/j.biocel.2006.08.015).

Record type: Article

Abstract

Osteonectin is a glycoprotein that modulates several aspects of cellular behaviour including proliferation and adhesion. The retinal pigment epithelium forms a continuous monolayer of polarised cells immediately bellow the neuroretina, and is integral to the homeostasis of photoreceptor cells. While osteonectin is expressed by normal retinal pigment epithelium in situ, its expression is significantly increased in retinal pigment epithelial cells associated with several common retinal diseases. This pattern of expression implies an important role for osteonectin in the biology of retinal pigment epithelial cells. However, the trafficking, processing, and eventual fate of osteonectin in these cells is not clear at present. Although the theoretical report of a leader sequence within the osteonectin open reading frame and its extracellular presence in some tissues indirectly support secretion of the protein, there is no direct experimental demonstration of the secretion route to date. As a first step towards understanding the role of osteonectin in retinal pigment epithelium, we studied the intracellular distribution and trafficking of the protein in living cells. Here, we present experimental evidence that a precursor osteonectin fusion protein is targeted to the endoplasmic reticulum/Golgi pathway, with a likely basal secretion in retinal pigment epithelial cells. In addition, we show that the precursor osteonectin protein having the leader sequence masked fails to undergo secretion leading to cell death, a phenotype which may be of relevance not only for retinal pathology, but also for other diseases such as the bone disorder known as pseudoachondroplasia that is associated with a lack of osteonectin secretion.

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More information

e-pub ahead of print date: 14 September 2006
Published date: 2007
Keywords: Achondroplasia, Cell Adhesion, Cell Death, Cell Line, Cell Polarity, Cell Proliferation, Golgi Apparatus, Humans, Osteonectin, Photoreceptor Cells, Pigment Epithelium of Eye, Protein Sorting Signals, Protein Transport, Recombinant Fusion Proteins, Journal Article, Research Support, Non-U.S. Gov't

Identifiers

Local EPrints ID: 422430
URI: http://eprints.soton.ac.uk/id/eprint/422430
ISSN: 1357-2725
PURE UUID: ce30bae5-4fda-460e-b8bb-4af3058325ef
ORCID for Arjuna Ratnayaka: ORCID iD orcid.org/0000-0002-1027-6938

Catalogue record

Date deposited: 24 Jul 2018 16:30
Last modified: 20 Jul 2019 00:38

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