Annexin A1 regulates hormone exocytosis through a mechanism involving actin reorganization.

The glucocorticoid-regulated protein annexin A1 is a potent inhibitor of hormone exocytosis in the neuroendocrine system, acting in a paracrine/juxtacrine manner. The signaling mechanism employed by annexin A1 in this process is uncertain, although we have recently presented evidence for a role of t...

Full description

Bibliographic Details
Main Authors: McArthur, S, Yazid, S, Christian, H, Sirha, R, Flower, R, Buckingham, J, Solito, E
Format: Journal article
Language:English
Published: 2009
_version_ 1797066626743402496
author McArthur, S
Yazid, S
Christian, H
Sirha, R
Flower, R
Buckingham, J
Solito, E
author_facet McArthur, S
Yazid, S
Christian, H
Sirha, R
Flower, R
Buckingham, J
Solito, E
author_sort McArthur, S
collection OXFORD
description The glucocorticoid-regulated protein annexin A1 is a potent inhibitor of hormone exocytosis in the neuroendocrine system, acting in a paracrine/juxtacrine manner. The signaling mechanism employed by annexin A1 in this process is uncertain, although we have recently presented evidence for a role of the formyl peptide receptor in vivo. We sought to characterize the mechanism of action of annexin A1 on exocytosis using the release of adrenocorticotrophin from the corticotroph-like cell line AtT20 as an in vitro model system. Through the comparison of adrenocorticotrophin release from cells expressing either wild-type annexin A1 or mutant forms, we show a critical involvement of phosphorylation on serine 27 and 45 in the translocation of the protein to the membrane and its inhibitory action on exocytosis. Moreover, we show, for the first time, that annexin A1-dependent inhibition of adrenocorticotrophin release involves the enhancement of actin polymerization to prevent exocytosis via formyl peptide receptor and Rho kinase signaling pathways. This finding has significant implications for the inhibitory actions of annexin A1 on exocytosis in other endocrine and immune contexts.
first_indexed 2024-03-06T21:44:42Z
format Journal article
id oxford-uuid:492813d2-2351-44fe-8c0f-d2ba039a1120
institution University of Oxford
language English
last_indexed 2024-03-06T21:44:42Z
publishDate 2009
record_format dspace
spelling oxford-uuid:492813d2-2351-44fe-8c0f-d2ba039a11202022-03-26T15:30:00ZAnnexin A1 regulates hormone exocytosis through a mechanism involving actin reorganization.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:492813d2-2351-44fe-8c0f-d2ba039a1120EnglishSymplectic Elements at Oxford2009McArthur, SYazid, SChristian, HSirha, RFlower, RBuckingham, JSolito, EThe glucocorticoid-regulated protein annexin A1 is a potent inhibitor of hormone exocytosis in the neuroendocrine system, acting in a paracrine/juxtacrine manner. The signaling mechanism employed by annexin A1 in this process is uncertain, although we have recently presented evidence for a role of the formyl peptide receptor in vivo. We sought to characterize the mechanism of action of annexin A1 on exocytosis using the release of adrenocorticotrophin from the corticotroph-like cell line AtT20 as an in vitro model system. Through the comparison of adrenocorticotrophin release from cells expressing either wild-type annexin A1 or mutant forms, we show a critical involvement of phosphorylation on serine 27 and 45 in the translocation of the protein to the membrane and its inhibitory action on exocytosis. Moreover, we show, for the first time, that annexin A1-dependent inhibition of adrenocorticotrophin release involves the enhancement of actin polymerization to prevent exocytosis via formyl peptide receptor and Rho kinase signaling pathways. This finding has significant implications for the inhibitory actions of annexin A1 on exocytosis in other endocrine and immune contexts.
spellingShingle McArthur, S
Yazid, S
Christian, H
Sirha, R
Flower, R
Buckingham, J
Solito, E
Annexin A1 regulates hormone exocytosis through a mechanism involving actin reorganization.
title Annexin A1 regulates hormone exocytosis through a mechanism involving actin reorganization.
title_full Annexin A1 regulates hormone exocytosis through a mechanism involving actin reorganization.
title_fullStr Annexin A1 regulates hormone exocytosis through a mechanism involving actin reorganization.
title_full_unstemmed Annexin A1 regulates hormone exocytosis through a mechanism involving actin reorganization.
title_short Annexin A1 regulates hormone exocytosis through a mechanism involving actin reorganization.
title_sort annexin a1 regulates hormone exocytosis through a mechanism involving actin reorganization
work_keys_str_mv AT mcarthurs annexina1regulateshormoneexocytosisthroughamechanisminvolvingactinreorganization
AT yazids annexina1regulateshormoneexocytosisthroughamechanisminvolvingactinreorganization
AT christianh annexina1regulateshormoneexocytosisthroughamechanisminvolvingactinreorganization
AT sirhar annexina1regulateshormoneexocytosisthroughamechanisminvolvingactinreorganization
AT flowerr annexina1regulateshormoneexocytosisthroughamechanisminvolvingactinreorganization
AT buckinghamj annexina1regulateshormoneexocytosisthroughamechanisminvolvingactinreorganization
AT solitoe annexina1regulateshormoneexocytosisthroughamechanisminvolvingactinreorganization