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Evidence for the role of adenosine 5’-triphosphate-binding cassette (ABC)-A1 in the externalization of Annexin 1 from pituitary folliculostellate cells and abca1-transfected cell models

Evidence for the role of adenosine 5’-triphosphate-binding cassette (ABC)-A1 in the externalization of Annexin 1 from pituitary folliculostellate cells and abca1-transfected cell models
Evidence for the role of adenosine 5’-triphosphate-binding cassette (ABC)-A1 in the externalization of Annexin 1 from pituitary folliculostellate cells and abca1-transfected cell models
Annexin 1 (ANXA1), a 37-kDa protein, is a member of the superfamily of Ca(2+)- and phospholipid-binding annexin proteins. In the anterior pituitary, ANXA1 is expressed mainly by folliculostellate (FS) cells and mediates the early delayed feedback inhibition exerted by glucocorticoids on the release of ACTH and other pituitary hormones. It has been previously demonstrated that TtT/GF cells (a FS cell line) express and externalize ANXA1 in response to glucocorticoid treatment. However, ANXA1 lacks a cleavable signal sequence and externalization is not affected by inhibitors of the secretory pathway. We have previously shown that glyburide, an ATP-binding cassette (ABC) transporter inhibitor, inhibits the externalization of ANXA1 from TtT/GF cells and pituitary tissue. Here we investigated whether ABCA1 is involved in ANXA1 externalization. The use of the ABCA1-transporter inhibitors geranyl-geranyl pyrophosphate and sulfobromophthalein significantly inhibited ANXA1 externalization. Partial silencing of ABCA1 expression in TtT/GF cells by siRNA also significantly decreased the amount of cell surface ANXA1. However, anterior pituitary tissue from ABCA1-null mice was found to externalize ANXA1 normally. Because compensation by other ABC family members may occur in vivo, ANXA1 externalization was studied in two transfection models: Xenopus oocytes injected with ABCA1 mRNA and AtT20 D1 corticoctroph cells cotransfected with ABCA1-green fluorescent protein and ANXA1. ABCA1-expressing oocytes, but not water-injected controls, were found to externalize ANXA1. Expression of ABCA1 in AtT20 D1 cells significantly increased the amount of cell surface ANXA1, compared with mock-transfected and ANXA1-only transfected controls. Together these data provide evidence for a role of ABCA1 in ANXA1 export.
0013-7227
3219-3227
Omer, Selma
c1a560b1-9b1f-4feb-8cda-555643ff9265
Meredith, David
52056084-4fcf-4b93-8b8b-23ff1e307667
Morris, John F.
5cb2036a-d7e1-4915-8d14-f476b12217ed
Christian, Helen C.
98497ac9-4d3a-4350-8283-dcd83a84207f
Omer, Selma
c1a560b1-9b1f-4feb-8cda-555643ff9265
Meredith, David
52056084-4fcf-4b93-8b8b-23ff1e307667
Morris, John F.
5cb2036a-d7e1-4915-8d14-f476b12217ed
Christian, Helen C.
98497ac9-4d3a-4350-8283-dcd83a84207f

Omer, Selma, Meredith, David, Morris, John F. and Christian, Helen C. (2006) Evidence for the role of adenosine 5’-triphosphate-binding cassette (ABC)-A1 in the externalization of Annexin 1 from pituitary folliculostellate cells and abca1-transfected cell models. Endocrinology, 147 (7), 3219-3227. (doi:10.1210/en.2006-0099). (PMID:16601136)

Record type: Article

Abstract

Annexin 1 (ANXA1), a 37-kDa protein, is a member of the superfamily of Ca(2+)- and phospholipid-binding annexin proteins. In the anterior pituitary, ANXA1 is expressed mainly by folliculostellate (FS) cells and mediates the early delayed feedback inhibition exerted by glucocorticoids on the release of ACTH and other pituitary hormones. It has been previously demonstrated that TtT/GF cells (a FS cell line) express and externalize ANXA1 in response to glucocorticoid treatment. However, ANXA1 lacks a cleavable signal sequence and externalization is not affected by inhibitors of the secretory pathway. We have previously shown that glyburide, an ATP-binding cassette (ABC) transporter inhibitor, inhibits the externalization of ANXA1 from TtT/GF cells and pituitary tissue. Here we investigated whether ABCA1 is involved in ANXA1 externalization. The use of the ABCA1-transporter inhibitors geranyl-geranyl pyrophosphate and sulfobromophthalein significantly inhibited ANXA1 externalization. Partial silencing of ABCA1 expression in TtT/GF cells by siRNA also significantly decreased the amount of cell surface ANXA1. However, anterior pituitary tissue from ABCA1-null mice was found to externalize ANXA1 normally. Because compensation by other ABC family members may occur in vivo, ANXA1 externalization was studied in two transfection models: Xenopus oocytes injected with ABCA1 mRNA and AtT20 D1 corticoctroph cells cotransfected with ABCA1-green fluorescent protein and ANXA1. ABCA1-expressing oocytes, but not water-injected controls, were found to externalize ANXA1. Expression of ABCA1 in AtT20 D1 cells significantly increased the amount of cell surface ANXA1, compared with mock-transfected and ANXA1-only transfected controls. Together these data provide evidence for a role of ABCA1 in ANXA1 export.

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e-pub ahead of print date: 23 March 2006
Published date: July 2006
Organisations: Faculty of Medicine

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Local EPrints ID: 388303
URI: http://eprints.soton.ac.uk/id/eprint/388303
ISSN: 0013-7227
PURE UUID: 05d9f093-7e3d-4337-91cf-5dc7bca74095

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Date deposited: 23 Feb 2016 11:53
Last modified: 15 Jul 2019 20:45

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Author: Selma Omer
Author: David Meredith
Author: John F. Morris
Author: Helen C. Christian

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