Ecdysone receptor isoform specific regulation of secretory granule acidification in the larval Drosophila salivary gland

Nagy, Anikó; Szenci, Győző; Boda, Attila; Al-Lami, Muna; Csizmadia, Tamás; Lőrincz, Péter; Juhász, Gábor; Lőw, Péter

doi:10.1016/j.ejcb.2022.151279

“…Maturation of SGs is a multidimensional process that involves homotypic fusion, acidification, cargo condensation, and acquisition of membrane proteins that will steer SGs to the apical plasma membrane and contribute to the recognition, tethering and fusion (Boda et al, 2023; Ji et al, 2018; Nagy et al, 2022; Syed, Zhang, Tran, Bleck, & Ten Hagen, 2022). In the current work, we have shown that the exocyst participates in several aspects of SG maturation.…”

Section: Discussionmentioning

confidence: 99%

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

Freire,

Pérez-Pandolfo,

Fresco

et al. 2023

Preprint

0

View full text Add to dashboard Cite

Eukaryotic cells depend on exocytosis to direct intracellularly synthesized material towards the extracellular space or the plasma membrane, so exocytosis constitutes a basic function for cellular homeostasis and communication between cells. The exocytic process comprises several steps that include biogenesis of the secretory granule (SG), maturation of the SG, and finally, its fusion with the plasma membrane, 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 graded 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.

show abstract

“…Maturation of SGs is a multidimensional process that involves homotypic fusion, acidification, cargo condensation, and acquisition of membrane proteins that will steer SGs to the apical plasma membrane and contribute to the recognition, tethering and fusion (Boda et al, 2023 ;Ji et al, 2018 ;Nagy et al, 2022 ;Syed, Zhang, Tran, Bleck, & Ten Hagen, 2022 ). In the current work, we have shown that the exocyst participates in several aspects of SG maturation.…”

Section: Discussionmentioning

confidence: 99%

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

Freire,

Pérez-Pandolfo,

Fresco

et al. 2023

Preprint

0

View full text Add to dashboard Cite

Eukaryotic cells depend on exocytosis to direct intracellularly synthesized material towards the extracellular space or the plasma membrane, so exocytosis constitutes a basic function for cellular homeostasis and communication between cells. The exocytic process comprises several steps that include biogenesis of the secretory granule (SG), maturation of the SG, and finally, its fusion with the plasma membrane, 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 graded 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.

show abstract

“…Drosophila larvae stop feeding 24 h after they enter the third instar larval stage, and concurrently the salivary glands start producing glue proteins that are packaged into SGs. These SGs mature over the next 18 h before they undergo synchronized exocytosis in response to a pulse of the steroid hormone ecdysone (Biyasheva et al, 2001;Burgess et al, 2011;Kamalesh et al, 2021;Nagy et al, 2022;Rousso et al, 2016;Tran et al, 2015). Because SGs store glue proteins, their release allows the pupal case to adhere onto a solid surface during metamorphosis.…”

Section: Introductionmentioning

confidence: 99%

Mutual dependence of Osbp and PI4KII in the maturation of regulated secretory granules

Ma,

Brill

2023

Preprint

0

View full text Add to dashboard Cite

Secretory granules (SGs) are crucial for normal animal physiology due to their role in regulated exocytosis of biologically active molecules. SG membranes are enriched in phosphatidylinositol 4-phosphate (PI4P) and cholesterol, and previous studies suggest lipid composition is important for SG biogenesis and function. Nonetheless, the molecular details of how lipids are regulated during SG biogenesis remain poorly understood. Here, we identify Oxysterol binding protein (Osbp) as a novel regulator of SG biogenesis in a Drosophila model. We show Osbp expression level positively correlates with SG size and that Osbp requires type II phosphatidylinositol 4-kinase (PI4KII) to increase SG size. Moreover, Osbp is needed for proper PI4KII and PI4P distribution, autophagic resolution and formation of cholesterol-rich endosomal tubules that are positive for PI4KII. Feeding larvae food supplemented with sterol leads to partial suppression of SG size and PI4P distribution defects in Osbp mutants. Our results indicate that reciprocal regulation of Osbp and PI4KII drives formation of membrane tubules that mediate SG maturation through elevating PI4P levels on SG membranes.

show abstract

Ecdysone receptor isoform specific regulation of secretory granule acidification in the larval Drosophila salivary gland

Cited by 8 publications

References 41 publications

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

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

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

Mutual dependence of Osbp and PI4KII in the maturation of regulated secretory granules

Contact Info

Product

Resources

About