The exocyst complex controls multiple events in the pathway of regulated exocytosis

Eukaryotic cells depend on exocytosis to direct intracellularly synthesized material toward the extracellular space or the plasma membrane, so exocytosis constitutes a basic function for cellular homeostasis and communication between cells. The secretory pathway includes biogenesis of secretory gran...

Full description

Saved in:
Bibliographic Details
Main Authors: Sofía Suárez Freire, Sebastián Perez-Pandolfo, Sabrina Micaela Fresco, Julián Valinoti, Eleonora Sorianello, Pablo Wappner, Mariana Melani
Format: Article
Language:English
Published: eLife Sciences Publications Ltd 2024-11-01
Series:eLife
Subjects:
Online Access:https://elifesciences.org/articles/92404
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1850268010164518912
author Sofía Suárez Freire
Sebastián Perez-Pandolfo
Sabrina Micaela Fresco
Julián Valinoti
Eleonora Sorianello
Pablo Wappner
Mariana Melani
author_facet Sofía Suárez Freire
Sebastián Perez-Pandolfo
Sabrina Micaela Fresco
Julián Valinoti
Eleonora Sorianello
Pablo Wappner
Mariana Melani
author_sort Sofía Suárez Freire
collection DOAJ
description Eukaryotic cells depend on exocytosis to direct intracellularly synthesized material toward the extracellular space or the plasma membrane, so exocytosis constitutes a basic function for cellular homeostasis and communication between cells. The secretory pathway includes biogenesis of secretory granules (SGs), their maturation and fusion with the plasma membrane (exocytosis), resulting in release of SG content to the extracellular space. The larval salivary gland of Drosophila melanogaster is an excellent model for studying exocytosis. This gland synthesizes mucins that are packaged in SGs that sprout from the trans-Golgi network and then undergo a maturation process that involves homotypic fusion, condensation, and acidification. Finally, mature SGs are directed to the apical domain of the plasma membrane with which they fuse, releasing their content into the gland lumen. The exocyst is a hetero-octameric complex that participates in tethering of vesicles to the plasma membrane during constitutive exocytosis. By precise temperature-dependent gradual activation of the Gal4-UAS expression system, we have induced different levels of silencing of exocyst complex subunits, and identified three temporarily distinctive steps of the regulated exocytic pathway where the exocyst is critically required: SG biogenesis, SG maturation, and SG exocytosis. Our results shed light on previously unidentified functions of the exocyst along the exocytic pathway. We propose that the exocyst acts as a general tethering factor in various steps of this cellular process.
format Article
id doaj-art-28b85813e0cf49b8aca342bc44ca576c
institution OA Journals
issn 2050-084X
language English
publishDate 2024-11-01
publisher eLife Sciences Publications Ltd
record_format Article
series eLife
spelling doaj-art-28b85813e0cf49b8aca342bc44ca576c2025-08-20T01:53:34ZengeLife Sciences Publications LtdeLife2050-084X2024-11-011210.7554/eLife.92404The exocyst complex controls multiple events in the pathway of regulated exocytosisSofía Suárez Freire0https://orcid.org/0009-0003-2908-3110Sebastián Perez-Pandolfo1Sabrina Micaela Fresco2Julián Valinoti3Eleonora Sorianello4Pablo Wappner5https://orcid.org/0000-0003-1517-0742Mariana Melani6https://orcid.org/0000-0002-9491-932XFundación Instituto Leloir, Buenos Aires, Argentina; Consejo Nacional De Investigaciones Científicas Y Técnicas (CONICET), Buenos Aries, ArgentinaFundación Instituto Leloir, Buenos Aires, Argentina; Consejo Nacional De Investigaciones Científicas Y Técnicas (CONICET), Buenos Aries, ArgentinaFundación Instituto Leloir, Buenos Aires, ArgentinaFundación Instituto Leloir, Buenos Aires, ArgentinaConsejo Nacional De Investigaciones Científicas Y Técnicas (CONICET), Buenos Aries, Argentina; Laboratorio de Regulación Hipofisaria, Instituto de Biología y Medicina Experimental (IBYME-CONICET), Buenos Aires, ArgentinaFundación Instituto Leloir, Buenos Aires, Argentina; Consejo Nacional De Investigaciones Científicas Y Técnicas (CONICET), Buenos Aries, Argentina; Departamento De Fisiología, Biología Molecular Y Celular, Facultad De Ciencias Exactas Y Naturales, Universidad De Buenos Aires, Buenos Aires, ArgentinaFundación Instituto Leloir, Buenos Aires, Argentina; Consejo Nacional De Investigaciones Científicas Y Técnicas (CONICET), Buenos Aries, Argentina; Departamento De Fisiología, Biología Molecular Y Celular, Facultad De Ciencias Exactas Y Naturales, Universidad De Buenos Aires, Buenos Aires, ArgentinaEukaryotic cells depend on exocytosis to direct intracellularly synthesized material toward the extracellular space or the plasma membrane, so exocytosis constitutes a basic function for cellular homeostasis and communication between cells. The secretory pathway includes biogenesis of secretory granules (SGs), their maturation and fusion with the plasma membrane (exocytosis), resulting in release of SG content to the extracellular space. The larval salivary gland of Drosophila melanogaster is an excellent model for studying exocytosis. This gland synthesizes mucins that are packaged in SGs that sprout from the trans-Golgi network and then undergo a maturation process that involves homotypic fusion, condensation, and acidification. Finally, mature SGs are directed to the apical domain of the plasma membrane with which they fuse, releasing their content into the gland lumen. The exocyst is a hetero-octameric complex that participates in tethering of vesicles to the plasma membrane during constitutive exocytosis. By precise temperature-dependent gradual activation of the Gal4-UAS expression system, we have induced different levels of silencing of exocyst complex subunits, and identified three temporarily distinctive steps of the regulated exocytic pathway where the exocyst is critically required: SG biogenesis, SG maturation, and SG exocytosis. Our results shed light on previously unidentified functions of the exocyst along the exocytic pathway. We propose that the exocyst acts as a general tethering factor in various steps of this cellular process.https://elifesciences.org/articles/92404exocytosisexocyst complextethering complexsecretory granuleDrosophila melanogaster
spellingShingle Sofía Suárez Freire
Sebastián Perez-Pandolfo
Sabrina Micaela Fresco
Julián Valinoti
Eleonora Sorianello
Pablo Wappner
Mariana Melani
The exocyst complex controls multiple events in the pathway of regulated exocytosis
eLife
exocytosis
exocyst complex
tethering complex
secretory granule
Drosophila melanogaster
title The exocyst complex controls multiple events in the pathway of regulated exocytosis
title_full The exocyst complex controls multiple events in the pathway of regulated exocytosis
title_fullStr The exocyst complex controls multiple events in the pathway of regulated exocytosis
title_full_unstemmed The exocyst complex controls multiple events in the pathway of regulated exocytosis
title_short The exocyst complex controls multiple events in the pathway of regulated exocytosis
title_sort exocyst complex controls multiple events in the pathway of regulated exocytosis
topic exocytosis
exocyst complex
tethering complex
secretory granule
Drosophila melanogaster
url https://elifesciences.org/articles/92404
work_keys_str_mv AT sofiasuarezfreire theexocystcomplexcontrolsmultipleeventsinthepathwayofregulatedexocytosis
AT sebastianperezpandolfo theexocystcomplexcontrolsmultipleeventsinthepathwayofregulatedexocytosis
AT sabrinamicaelafresco theexocystcomplexcontrolsmultipleeventsinthepathwayofregulatedexocytosis
AT julianvalinoti theexocystcomplexcontrolsmultipleeventsinthepathwayofregulatedexocytosis
AT eleonorasorianello theexocystcomplexcontrolsmultipleeventsinthepathwayofregulatedexocytosis
AT pablowappner theexocystcomplexcontrolsmultipleeventsinthepathwayofregulatedexocytosis
AT marianamelani theexocystcomplexcontrolsmultipleeventsinthepathwayofregulatedexocytosis
AT sofiasuarezfreire exocystcomplexcontrolsmultipleeventsinthepathwayofregulatedexocytosis
AT sebastianperezpandolfo exocystcomplexcontrolsmultipleeventsinthepathwayofregulatedexocytosis
AT sabrinamicaelafresco exocystcomplexcontrolsmultipleeventsinthepathwayofregulatedexocytosis
AT julianvalinoti exocystcomplexcontrolsmultipleeventsinthepathwayofregulatedexocytosis
AT eleonorasorianello exocystcomplexcontrolsmultipleeventsinthepathwayofregulatedexocytosis
AT pablowappner exocystcomplexcontrolsmultipleeventsinthepathwayofregulatedexocytosis
AT marianamelani exocystcomplexcontrolsmultipleeventsinthepathwayofregulatedexocytosis