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The pro-hormone secretogranin II regulates dense-core secretory granule biogenesis in catecholaminergic cells

The pro-hormone secretogranin II regulates dense-core secretory granule biogenesis in catecholaminergic cells
The pro-hormone secretogranin II regulates dense-core secretory granule biogenesis in catecholaminergic cells
Processes underlying the formation of dense core secretory granules (DCGs) of neuroendocrine cells are poorly understood. Here, we present evidence that DCG biogenesis is dependent on the secretory protein secretogranin (Sg) II, a member of the granin family of pro-hormone cargo of DCGs in neuroendocrine cells. Depletion of SgII expression in PC12 cells leads to a decrease in both the number and size of DCGs and impairs DCG trafficking of other regulated hormones. Expression of SgII fusion proteins in a secretory-deficient PC12 variant rescues a regulated secretory pathway. SgII-containing dense core vesicles share morphological and physical properties with bona fide DCGs, are competent for regulated exocytosis, and maintain an acidic luminal pH through the V-type H+-translocating ATPase. The granulogenic activity of SgII requires a pH gradient along this secretory pathway. We conclude that SgII is a critical factor for the regulation of DCG biogenesis in neuroendocrine cells, mediating the formation of functional DCGs via its pH-dependent aggregation at the trans-Golgi network.
1083-351X
10030-10043
Courel, Maïté
814de790-8c9c-43dd-b546-bdfa77b6c510
Soler-Jover, Alex
d866ba66-2068-4c83-9ff0-658d98d9783a
Rodriguez-Flores, Juan L.
6c77391b-827f-427c-9b01-c0b0f99889f4
Mahata, Sushil K.
75a462f0-3564-46ff-b34a-5de54eaa1884
Elias, Salah
a9b11116-8efb-44b3-8241-2f0f2af847c3
Montero-Hadjadje, Maïté
b4197bb1-ab85-4c82-8285-09cfff390d4f
Anouar, Youssef
a19c61e2-e59d-417f-981b-f88eccf492b2
Giuly, Richard J.
4821b05b-0c05-4f70-800c-ab94cebe829f
O'Connor, Daniel T.
35833fbc-9ade-4f0e-a27a-e7c1b4c5ff64
Taupenot, Laurent
a34ec37f-20d9-4473-82e3-0da10f52ea78
Courel, Maïté
814de790-8c9c-43dd-b546-bdfa77b6c510
Soler-Jover, Alex
d866ba66-2068-4c83-9ff0-658d98d9783a
Rodriguez-Flores, Juan L.
6c77391b-827f-427c-9b01-c0b0f99889f4
Mahata, Sushil K.
75a462f0-3564-46ff-b34a-5de54eaa1884
Elias, Salah
a9b11116-8efb-44b3-8241-2f0f2af847c3
Montero-Hadjadje, Maïté
b4197bb1-ab85-4c82-8285-09cfff390d4f
Anouar, Youssef
a19c61e2-e59d-417f-981b-f88eccf492b2
Giuly, Richard J.
4821b05b-0c05-4f70-800c-ab94cebe829f
O'Connor, Daniel T.
35833fbc-9ade-4f0e-a27a-e7c1b4c5ff64
Taupenot, Laurent
a34ec37f-20d9-4473-82e3-0da10f52ea78

Courel, Maïté, Soler-Jover, Alex, Rodriguez-Flores, Juan L., Mahata, Sushil K., Elias, Salah, Montero-Hadjadje, Maïté, Anouar, Youssef, Giuly, Richard J., O'Connor, Daniel T. and Taupenot, Laurent (2010) The pro-hormone secretogranin II regulates dense-core secretory granule biogenesis in catecholaminergic cells. The Journal of Biological Chemistry, 285 (13), 10030-10043. (doi:10.1074/jbc.M109.064196).

Record type: Article

Abstract

Processes underlying the formation of dense core secretory granules (DCGs) of neuroendocrine cells are poorly understood. Here, we present evidence that DCG biogenesis is dependent on the secretory protein secretogranin (Sg) II, a member of the granin family of pro-hormone cargo of DCGs in neuroendocrine cells. Depletion of SgII expression in PC12 cells leads to a decrease in both the number and size of DCGs and impairs DCG trafficking of other regulated hormones. Expression of SgII fusion proteins in a secretory-deficient PC12 variant rescues a regulated secretory pathway. SgII-containing dense core vesicles share morphological and physical properties with bona fide DCGs, are competent for regulated exocytosis, and maintain an acidic luminal pH through the V-type H+-translocating ATPase. The granulogenic activity of SgII requires a pH gradient along this secretory pathway. We conclude that SgII is a critical factor for the regulation of DCG biogenesis in neuroendocrine cells, mediating the formation of functional DCGs via its pH-dependent aggregation at the trans-Golgi network.

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More information

e-pub ahead of print date: 8 January 2010
Published date: 26 March 2010
Organisations: Biomedicine

Identifiers

Local EPrints ID: 408033
URI: http://eprints.soton.ac.uk/id/eprint/408033
ISSN: 1083-351X
PURE UUID: 5441456d-637b-4641-9c5b-b55b806e3fe3
ORCID for Salah Elias: ORCID iD orcid.org/0000-0003-1005-438X

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Date deposited: 10 May 2017 01:04
Last modified: 16 Mar 2024 04:29

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Contributors

Author: Maïté Courel
Author: Alex Soler-Jover
Author: Juan L. Rodriguez-Flores
Author: Sushil K. Mahata
Author: Salah Elias ORCID iD
Author: Maïté Montero-Hadjadje
Author: Youssef Anouar
Author: Richard J. Giuly
Author: Daniel T. O'Connor
Author: Laurent Taupenot

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