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Investigating the role of ABCA1 in the externalisation of Annexin 1 in the anterior pituitary

Investigating the role of ABCA1 in the externalisation of Annexin 1 in the anterior pituitary
Investigating the role of ABCA1 in the externalisation of Annexin 1 in the anterior pituitary
Annexin 1 (Anx-1), a 37kDa protein, is a member of the super-family of Ca 2+ and phospholipid-binding annexin proteins and acts as a mediator of glucocorticoid (GC) action in the host defense and neuroendocrine systems. In the anterior pituitary Anx-1 is expressed mainly by folliculostellate (FS) cells and mediates the early delayed feedback inhibition exerted by GCs on the release of ACTH and other pituitary hormones. It has been previously demonstrated that TtT/GF cells (mouse pituitary-derived FS cells) express and externalize Anx-1 in response to GC 1. However, Anx-1 lacks a cleavable signal sequence and the externalization was not affected by inhibitors of the secretory pathway 2. We have previously shown that glyburide, an inhibitor of ATP-binding cassette (ABC) transporters inhibited the externalization of Anx-1 from TtT/GF cells 3. Here we investigated the mechanism of Anx-1 externalization from TtT/GF cells by ABCA1. Unlike glyburide, the use of selective ABCA1 inhibitors such as geranyl-geranyl pyrophosphate (GGPP) and sulfobromopthalein (SBP) did not markedly decrease Anx-1 externalization. Furthermore, it was found that silencing ABCA1 expression in TtT/GF cells by siRNA did not affect Anx-1 externalization. This was further confirmed by investigating Anx-1 externalization from pituitaries from ABCA1 knock out mice, where the knockout mice were found to externalize Anx-1 normally. However, since compensation by other ABC family members may occur in vivo, Anx-1 externalization was studied in zenopus oocytes injected with ABCA1 mRNA. The ABCA1 expressing oocytes were found to efficiently externalize endogenous Anx-1 providing good evidence for a role of ABCA1 in Anx-1 export
Omer, S.
c1a560b1-9b1f-4feb-8cda-555643ff9265
Christian, H.C.
6d8fa111-286d-47fc-95d3-bfefc17e5527
Morris, J.F.
e471889e-fb79-483d-a424-cf55a1754e36
Omer, S.
c1a560b1-9b1f-4feb-8cda-555643ff9265
Christian, H.C.
6d8fa111-286d-47fc-95d3-bfefc17e5527
Morris, J.F.
e471889e-fb79-483d-a424-cf55a1754e36

Omer, S., Christian, H.C. and Morris, J.F. (2005) Investigating the role of ABCA1 in the externalisation of Annexin 1 in the anterior pituitary. 196th Meeting for the Society for Endocrinology, London, United Kingdom. 07 - 09 Nov 2005.

Record type: Conference or Workshop Item (Paper)

Abstract

Annexin 1 (Anx-1), a 37kDa protein, is a member of the super-family of Ca 2+ and phospholipid-binding annexin proteins and acts as a mediator of glucocorticoid (GC) action in the host defense and neuroendocrine systems. In the anterior pituitary Anx-1 is expressed mainly by folliculostellate (FS) cells and mediates the early delayed feedback inhibition exerted by GCs on the release of ACTH and other pituitary hormones. It has been previously demonstrated that TtT/GF cells (mouse pituitary-derived FS cells) express and externalize Anx-1 in response to GC 1. However, Anx-1 lacks a cleavable signal sequence and the externalization was not affected by inhibitors of the secretory pathway 2. We have previously shown that glyburide, an inhibitor of ATP-binding cassette (ABC) transporters inhibited the externalization of Anx-1 from TtT/GF cells 3. Here we investigated the mechanism of Anx-1 externalization from TtT/GF cells by ABCA1. Unlike glyburide, the use of selective ABCA1 inhibitors such as geranyl-geranyl pyrophosphate (GGPP) and sulfobromopthalein (SBP) did not markedly decrease Anx-1 externalization. Furthermore, it was found that silencing ABCA1 expression in TtT/GF cells by siRNA did not affect Anx-1 externalization. This was further confirmed by investigating Anx-1 externalization from pituitaries from ABCA1 knock out mice, where the knockout mice were found to externalize Anx-1 normally. However, since compensation by other ABC family members may occur in vivo, Anx-1 externalization was studied in zenopus oocytes injected with ABCA1 mRNA. The ABCA1 expressing oocytes were found to efficiently externalize endogenous Anx-1 providing good evidence for a role of ABCA1 in Anx-1 export

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Published date: 8 November 2005
Venue - Dates: 196th Meeting for the Society for Endocrinology, London, United Kingdom, 2005-11-07 - 2005-11-09
Organisations: Faculty of Medicine

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Local EPrints ID: 388309
URI: http://eprints.soton.ac.uk/id/eprint/388309
PURE UUID: afb87ebf-b5ff-4a1d-a74a-9b4a0a6339d0

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Date deposited: 23 Feb 2016 13:43
Last modified: 14 Jul 2020 16:36

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Contributors

Author: S. Omer
Author: H.C. Christian
Author: J.F. Morris

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