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Chromogranin A Induces the biogenesis of granules with calcium- and actin-dependent dynamics and exocytosis in constitutively secreting cells

Chromogranin A Induces the biogenesis of granules with calcium- and actin-dependent dynamics and exocytosis in constitutively secreting cells
Chromogranin A Induces the biogenesis of granules with calcium- and actin-dependent dynamics and exocytosis in constitutively secreting cells
Chromogranins are a family of acidic glycoproteins that play an active role in hormone and neuropeptide secretion through their crucial role in secretory granule biogenesis in neuroendocrine cells. However, the molecular mechanisms underlying their granulogenic activity are still not fully understood. Because we previously demonstrated that the expression of the major component of secretory granules, chromogranin A (CgA), is able to induce the formation of secretory granules in nonendocrine COS-7 cells, we decided to use this model to dissect the mechanisms triggered by CgA leading to the biogenesis and trafficking of such granules. Using quantitative live cell imaging, we first show that CgA-induced organelles exhibit a Ca2+-dependent trafficking, in contrast to native vesicle stomatitis virus G protein-containing constitutive vesicles. To identify the proteins that confer such properties to the newly formed granules, we developed CgA-stably-expressing COS-7 cells, purified their CgA-containing granules by subcellular fractionation, and analyzed the granule proteome by liquid chromatography-tandem mass spectrometry. This analysis revealed the association of several cytosolic proteins to the granule membrane, including GTPases, cytoskeleton-based molecular motors, and other proteins with actin- and/or Ca2+-binding properties. Furthermore, disruption of cytoskeleton affects not only the distribution and the transport but also the Ca2+-evoked exocytosis of the CgA-containing granules, indicating that these granules interact with microtubules and cortical actin for the regulated release of their content. These data demonstrate for the first time that the neuroendocrine factor CgA induces the recruitment of cytoskeleton-, GTP-, and Ca2+-binding proteins in constitutively secreting COS-7 cells to generate vesicles endowed with typical dynamics and exocytotic properties of neuroendocrine secretory granules.
0013-7227
4444-4456
Elias, Salah
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Delestre, Charlène
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Ory, Stéphane
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Marais, Sébastien
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Courel, Maïté
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Vazquez-Martinez, Rafael
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Bernard, Sophie
b2317dda-fac6-424b-9640-486c9e3d8653
Coquet, Laurent
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Malagon, Maria M.
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Driouich, Azeddine
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Chan, Philippe
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Gasman, Stéphane
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Anouar, Youssef
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Montero-Hadjadje, Maïté
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Elias, Salah
a9b11116-8efb-44b3-8241-2f0f2af847c3
Delestre, Charlène
1a958b45-ab5a-4c33-a0ae-4763d34313b2
Ory, Stéphane
82184670-67c2-4548-bf4b-c98403818efa
Marais, Sébastien
afaf9684-c41e-4295-8ecc-0323cbd8d27e
Courel, Maïté
945d57c1-8ba0-41ab-8076-c995071b729e
Vazquez-Martinez, Rafael
eee6637c-d610-4ff1-b6c5-0f9590d18057
Bernard, Sophie
b2317dda-fac6-424b-9640-486c9e3d8653
Coquet, Laurent
81117148-fa61-4beb-aa8f-ea2bbe2a4ce2
Malagon, Maria M.
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Driouich, Azeddine
7acbe6b9-7965-44fa-a121-f1ae7cb33e68
Chan, Philippe
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Gasman, Stéphane
e250f899-7a2e-4866-89bf-9a3bb4e2eb9d
Anouar, Youssef
a19c61e2-e59d-417f-981b-f88eccf492b2
Montero-Hadjadje, Maïté
b4197bb1-ab85-4c82-8285-09cfff390d4f

Elias, Salah, Delestre, Charlène, Ory, Stéphane, Marais, Sébastien, Courel, Maïté, Vazquez-Martinez, Rafael, Bernard, Sophie, Coquet, Laurent, Malagon, Maria M., Driouich, Azeddine, Chan, Philippe, Gasman, Stéphane, Anouar, Youssef and Montero-Hadjadje, Maïté (2012) Chromogranin A Induces the biogenesis of granules with calcium- and actin-dependent dynamics and exocytosis in constitutively secreting cells. Endocrinology, 153 (9), 4444-4456. (doi:10.1210/en.2012-1436).

Record type: Article

Abstract

Chromogranins are a family of acidic glycoproteins that play an active role in hormone and neuropeptide secretion through their crucial role in secretory granule biogenesis in neuroendocrine cells. However, the molecular mechanisms underlying their granulogenic activity are still not fully understood. Because we previously demonstrated that the expression of the major component of secretory granules, chromogranin A (CgA), is able to induce the formation of secretory granules in nonendocrine COS-7 cells, we decided to use this model to dissect the mechanisms triggered by CgA leading to the biogenesis and trafficking of such granules. Using quantitative live cell imaging, we first show that CgA-induced organelles exhibit a Ca2+-dependent trafficking, in contrast to native vesicle stomatitis virus G protein-containing constitutive vesicles. To identify the proteins that confer such properties to the newly formed granules, we developed CgA-stably-expressing COS-7 cells, purified their CgA-containing granules by subcellular fractionation, and analyzed the granule proteome by liquid chromatography-tandem mass spectrometry. This analysis revealed the association of several cytosolic proteins to the granule membrane, including GTPases, cytoskeleton-based molecular motors, and other proteins with actin- and/or Ca2+-binding properties. Furthermore, disruption of cytoskeleton affects not only the distribution and the transport but also the Ca2+-evoked exocytosis of the CgA-containing granules, indicating that these granules interact with microtubules and cortical actin for the regulated release of their content. These data demonstrate for the first time that the neuroendocrine factor CgA induces the recruitment of cytoskeleton-, GTP-, and Ca2+-binding proteins in constitutively secreting COS-7 cells to generate vesicles endowed with typical dynamics and exocytotic properties of neuroendocrine secretory granules.

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Published date: 1 September 2012
Organisations: Biomedicine

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Local EPrints ID: 408034
URI: http://eprints.soton.ac.uk/id/eprint/408034
ISSN: 0013-7227
PURE UUID: b912e54c-e1dc-4747-a43e-16576dc9dc73

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Date deposited: 10 May 2017 01:04
Last modified: 25 Sep 2019 16:32

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Contributors

Author: Salah Elias
Author: Charlène Delestre
Author: Stéphane Ory
Author: Sébastien Marais
Author: Maïté Courel
Author: Rafael Vazquez-Martinez
Author: Sophie Bernard
Author: Laurent Coquet
Author: Maria M. Malagon
Author: Azeddine Driouich
Author: Philippe Chan
Author: Stéphane Gasman
Author: Youssef Anouar
Author: Maïté Montero-Hadjadje

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