scholarly journals The TRAPP complex mediates secretion arrest induced by stress granule assembly

2019 ◽  
Author(s):  
Francesca Zappa ◽  
Cathal Wilson ◽  
Giuseppe Di Tullio ◽  
Michele Santoro ◽  
Piero Pucci ◽  
...  
Keyword(s):  
Membrane Trafficking ◽  
Secretory Pathway ◽  
Acute Stress ◽  
Stress Exposure ◽  
Proliferating Cells ◽  
Early Secretory Pathway ◽  
Er Exit Sites ◽  
Protein Particle ◽  
Mediate Cell ◽  
Er Export

The TRAnsport-Protein-Particle (TRAPP) complex controls multiple membrane trafficking steps and is thus strategically positioned to mediate cell adaptation to diverse environmental conditions, including acute stress. We have identified TRAPP as a key component of a branch of the integrated stress response that impinges on the early secretory pathway. TRAPP associates with and drives the recruitment of the COPII coat to stress granules (SGs) leading to vesiculation of the Golgi complex and an arrest of ER export. Interestingly, the relocation of TRAPP and COPII to SGs only occurs in actively proliferating cells and is CDK1/2-dependent. We show that CDK1/2 activity controls the COPII cycle at ER exit sites (ERES) and that its inhibition prevents TRAPP/COPII relocation to SGs by stabilizing them at the ERES. Importantly, TRAPP is not just a passive constituent of SGs but controls their maturation since SGs that assemble in TRAPP-depleted cells are smaller and are no longer able to recruit RACK1 and Raptor, rendering the cells more prone to undergo apoptosis upon stress exposure.

scholarly journals MAPK signaling to the early secretory pathway revealed by kinase/phosphatase functional screening

2010 ◽  
Vol 189 (6) ◽  
pp. 997-1011 ◽  
Author(s):  
Hesso Farhan ◽  
Markus W. Wendeler ◽  
Sandra Mitrovic ◽  
Eugenio Fava ◽  
Yael Silberberg ◽  
...  
Keyword(s):  
Protein Trafficking ◽  
Secretory Pathway ◽  
Mapk Signaling ◽  
Functional Screening ◽  
Growth Factor Signaling ◽  
Early Secretory Pathway ◽  
Kinase Suppressor Of Ras ◽  
Er Exit Sites ◽  
Vesicle Biogenesis ◽  
Er Export

To what extent the secretory pathway is regulated by cellular signaling is unknown. In this study, we used RNA interference to explore the function of human kinases and phosphatases in controlling the organization of and trafficking within the secretory pathway. We identified 122 kinases/phosphatases that affect endoplasmic reticulum (ER) export, ER exit sites (ERESs), and/or the Golgi apparatus. Numerous kinases/phosphatases regulate the number of ERESs and ER to Golgi protein trafficking. Among the pathways identified, the Raf–MEK (MAPK/ERK [extracellular signal-regulated kinase] kinase)–ERK cascade, including its regulatory proteins CNK1 (connector enhancer of the kinase suppressor of Ras-1) and neurofibromin, controls the number of ERESs via ERK2, which targets Sec16, a key regulator of ERESs and COPII (coat protein II) vesicle biogenesis. Our analysis reveals an unanticipated complexity of kinase/phosphatase-mediated regulation of the secretory pathway, uncovering a link between growth factor signaling and ER export.

scholarly journals A stress assembly that confers cell viability by preserving ERES components during amino-acid starvation

eLife ◽  
2014 ◽  
Vol 3 ◽  
Author(s):  
Margarita Zacharogianni ◽  
Angelica Aguilera-Gomez ◽  
Tineke Veenendaal ◽  
Jan Smout ◽  
Catherine Rabouille
Keyword(s):  
Amino Acid ◽  
Cell Viability ◽  
Secretory Pathway ◽  
Protein Transport ◽  
Liquid Droplet ◽  
Protein Translation ◽  
Amino Acid Starvation ◽  
Early Secretory Pathway ◽  
Er Exit Sites ◽  
Nutritional Restriction

Nutritional restriction leads to protein translation attenuation that results in the storage and degradation of free mRNAs in cytoplasmic assemblies. In this study, we show in Drosophila S2 cells that amino-acid starvation also leads to the inhibition of another major anabolic pathway, the protein transport through the secretory pathway, and to the formation of a novel reversible non-membrane bound stress assembly, the Sec body that incorporates components of the ER exit sites. Sec body formation does not depend on membrane traffic in the early secretory pathway, yet requires both Sec23 and Sec24AB. Sec bodies have liquid droplet-like properties, and they act as a protective reservoir for ERES components to rebuild a functional secretory pathway after re-addition of amino-acids acting as a part of a survival mechanism. Taken together, we propose that the formation of these structures is a novel stress response mechanism to provide cell viability during and after nutrient stress.

scholarly journals Streamlined Architecture and Glycosylphosphatidylinositol-dependent Trafficking in the Early Secretory Pathway of African Trypanosomes

2009 ◽  
Vol 20 (22) ◽  
pp. 4739-4750 ◽  
Author(s):  
Elitza S. Sevova ◽  
James D. Bangs
Keyword(s):  
Secretory Pathway ◽  
Matrix Protein ◽  
Dominant Negative ◽  
Surface Glycoprotein ◽  
African Trypanosomes ◽  
Early Secretory Pathway ◽  
Dominant Negative Mutation ◽  
Er Exit Sites ◽  
Copii Vesicles ◽  
Golgi Matrix

The variant surface glycoprotein (VSG) of bloodstream form Trypanosoma brucei (Tb) is a critical virulence factor. The VSG glycosylphosphatidylinositol (GPI)-anchor strongly influences passage through the early secretory pathway. Using a dominant-negative mutation of TbSar1, we show that endoplasmic reticulum (ER) exit of secretory cargo in trypanosomes is dependent on the coat protein complex II (COPII) machinery. Trypanosomes have two orthologues each of the Sec23 and Sec24 COPII subunits, which form specific heterodimeric pairs: TbSec23.1/TbSec24.2 and TbSec23.2/TbSec24.1. RNA interference silencing of each subunit is lethal but has minimal effects on trafficking of soluble and transmembrane proteins. However, silencing of the TbSec23.2/TbSec24.1 pair selectively impairs ER exit of GPI-anchored cargo. All four subunits colocalize to one or two ER exit sites (ERES), in close alignment with the postnuclear flagellar adherence zone (FAZ), and closely juxtaposed to corresponding Golgi clusters. These ERES are nucleated on the FAZ-associated ER. The Golgi matrix protein Tb Golgi reassembly stacking protein defines a region between the ERES and Golgi, suggesting a possible structural role in the ERES:Golgi junction. Our results confirm a selective mechanism for GPI-anchored cargo loading into COPII vesicles and a remarkable degree of streamlining in the early secretory pathway. This unusual architecture probably maximizes efficiency of VSG transport and fidelity in organellar segregation during cytokinesis.

scholarly journals The Secretory Apparatus of an Ancient Eukaryote: Protein Sorting to Separate Export Pathways Occurs Before Formation of Transient Golgi-like Compartments

2003 ◽  
Vol 14 (4) ◽  
pp. 1433-1447 ◽  
Author(s):  
Matthias Marti ◽  
Yajie Li ◽  
Elisabeth M. Schraner ◽  
Peter Wild ◽  
Peter Köhler ◽  
...  
Keyword(s):  
Secretory Pathway ◽  
Protein Sorting ◽  
Protozoan Parasite ◽  
Retrograde Transport ◽  
Surface Proteins ◽  
Cyst Form ◽  
Early Secretory Pathway ◽  
Vertebrate Hosts ◽  
Er Export ◽  
Secretory Apparatus

Transmission of the protozoan parasite Giardia intestinalis to vertebrate hosts presupposes the encapsulation of trophozoites into an environmentally resistant and infectious cyst form. We have previously shown that cyst wall proteins were faithfully sorted to large encystation-specific vesicles (ESVs), despite the absence of a recognizable Golgi apparatus. Here, we demonstrate that sorting to a second constitutively active pathway transporting variant-specific surface proteins (VSPs) to the surface depended on the cytoplasmic VSP tail. Moreover, pulsed endoplasmic reticulum (ER) export of chimeric reporters containing functional signals for both pathways showed that protein sorting was done at or very soon after export from the ER. Correspondingly, we found that a limited number of novel transitional ER-like structures together with small transport intermediates were generated during encystation. Colocalization of transitional ER regions and early ESVs with coat protein (COP) II and of maturing ESVs with COPI and clathrin strongly suggested that ESVs form by fusion of ER-derived vesicles and subsequently undergo maturation by retrograde transport. Together, the data supported the hypothesis that in Giardia, a primordial secretory apparatus is in operation by which proteins are sorted in the early secretory pathway, and the developmentally induced ESVs carry out at least some Golgi functions.

Mammalian GPI-anchored proteins require p24 proteins for their efficient transport from the ER to the plasma membrane

2007 ◽  
Vol 409 (2) ◽  
pp. 555-562 ◽  
Author(s):  
Satoshi Takida ◽  
Yusuke Maeda ◽  
Taroh Kinoshita
Keyword(s):  
Plasma Membrane ◽  
Membrane Trafficking ◽  
Secretory Pathway ◽  
Direct Evidence ◽  
Temperature Sensitive ◽  
Early Secretory Pathway ◽  
Cargo Proteins ◽  
Transport Vesicle ◽  
A Cell ◽  
P24 Proteins

The GPI (glycosylphosphatidylinositol) moiety is attached to newly synthesized proteins in the lumen of the ER (endoplasmic reticulum). The modified proteins are then directed to the PM (plasma membrane). Less well understood is how nascent mammalian GPI-anchored proteins are targeted from the ER to the PM. In the present study, we investigated mechanisms underlying membrane trafficking of the GPI-anchored proteins, focusing on the early secretory pathway. We first established a cell line that stably expresses inducible temperature-sensitive GPI-fused proteins as a reporter and examined roles of transport-vesicle constituents called p24 proteins in the traffic of the GPI-anchored proteins. We selectively suppressed one of the p24 proteins, namely p23, employing RNAi (RNA interference) techniques. The suppression resulted in pronounced delays of PM expression of the GPI-fused reporter proteins. Furthermore, maturation of DAF (decay-accelerating factor), one of the GPI-anchored proteins in mammals, was slowed by the suppression of p23, indicating delayed trafficking of DAF from the ER to the Golgi. Trafficking of non-GPI-linked cargo proteins was barely affected by p23 knockdown. This is the first to demonstrate direct evidence for the transport of mammalian GPI-anchored proteins being mediated by p24 proteins.

Defects in early secretory pathway transport machinery components and neurodevelopmental disorders

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Bor Luen Tang
Keyword(s):  
Membrane Trafficking ◽  
Mammalian Cells ◽  
Secretory Pathway ◽  
Underlying Disease ◽  
Membrane Dynamics ◽  
Coat Proteins ◽  
Disease Manifestation ◽  
Vesicular Traffic ◽  
Early Secretory Pathway ◽  
Genes Encoding

Abstract The early secretory pathway, provisionally comprising of vesicular traffic between the endoplasmic reticulum (ER) and the Golgi apparatus, occurs constitutively in mammalian cells. Critical for a constant supply of secretory and plasma membrane (PM) materials, the pathway is presumably essential for general cellular function and survival. Neurons exhibit a high intensity in membrane dynamics and protein/lipid trafficking, with differential and polarized trafficking towards the somatodendritic and axonal PM domains. Mutations in genes encoding early secretory pathway membrane trafficking machinery components are known to result in neurodevelopmental or neurological disorders with disease manifestation in early life. Here, such rare disorders associated with autosomal recessive mutations in coat proteins, membrane tethering complexes and membrane fusion machineries responsible for trafficking in the early secretory pathway are summarily discussed. These mutations affected genes encoding subunits of coat protein complex I and II, subunits of transport protein particle (TRAPP) complexes, members of the YIP1 domain family (YIPF) and a SNAP receptor (SNARE) family member. Why the ubiquitously present and constitutively acting early secretory pathway machinery components could specifically affect neurodevelopment is addressed, with the plausible underlying disease etiologies and neuropathological mechanisms resulting from these mutations explored.

scholarly journals Branched Actin Maintains Acetylated Microtubule Network in the Early Secretory Pathway

Cells ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 15
Author(s):  
Azumi Yoshimura ◽  
Stéphanie Miserey-Lenkei ◽  
Evelyne Coudrier ◽  
Bruno Goud
Keyword(s):  
Golgi Apparatus ◽  
Transport Process ◽  
Actin Polymerization ◽  
Secretory Pathway ◽  
Microtubule Network ◽  
Early Secretory Pathway ◽  
Golgi Transport ◽  
Er Exit Sites ◽  
Intermediate Compartment ◽  
Stable Network

In the early secretory pathway, the delivery of anterograde cargoes from the endoplasmic reticulum (ER) exit sites (ERES) to the Golgi apparatus is a multi-step transport process occurring via the ER-Golgi intermediate compartment (IC, also called ERGIC). While the role microtubules in ER-to-Golgi transport has been well established, how the actin cytoskeleton contributes to this process remains poorly understood. Here, we report that Arp2/3 inhibition affects the network of acetylated microtubules around the Golgi and induces the accumulation of unusually long RAB1/GM130-positive carriers around the centrosome. These long carriers are less prone to reach the Golgi apparatus, and arrival of anterograde cargoes to the Golgi is decreased upon Arp2/3 inhibition. Our data suggest that Arp2/3-dependent actin polymerization maintains a stable network of acetylated microtubules, which ensures efficient cargo trafficking at the late stage of ER to Golgi transport.

scholarly journals Modulation of the secretory pathway by amino-acid starvation

2018 ◽  
Vol 217 (7) ◽  
pp. 2261-2271 ◽  
Author(s):  
Wessel van Leeuwen ◽  
Felix van der Krift ◽  
Catherine Rabouille
Keyword(s):  
Amino Acid ◽  
Secretory Pathway ◽  
Amino Acid Starvation ◽  
Mechanistic Target Of Rapamycin ◽  
Early Secretory Pathway ◽  
Surrounding Environment ◽  
Major Nutrient ◽  
Er Exit Sites ◽  
Anabolic Pathway

As a major anabolic pathway, the secretory pathway needs to adapt to the demands of the surrounding environment and responds to different exogenous signals and stimuli. In this context, the transport in the early secretory pathway from the endoplasmic reticulum (ER) to the Golgi apparatus appears particularly regulated. For instance, protein export from the ER is critically stimulated by growth factors. Conversely, nutrient starvation also modulates functions of the early secretory pathway in multiple ways. In this review, we focus on amino-acid starvation and how the function of the early secretory pathway is redirected to fuel autophagy, how the ER exit sites are remodeled into novel cytoprotective stress assemblies, and how secretion is modulated in vivo in starving organisms. With the increasingly exciting knowledge on mechanistic target of rapamycin complex 1 (mTORC1), the major nutrient sensor, it is also a good moment to establish how the modulation of the secretory pathway by amino-acid restriction intersects with this major signaling hub.

Lectins and protein traffic early in the secretory pathway

2002 ◽  
Vol 69 ◽  
pp. 73-82 ◽  
Author(s):  
Hans-Peter Hauri ◽  
Oliver Nufer ◽  
Lionel Breuza ◽  
Houchaima Ben Tekaya ◽  
Lu Liang
Keyword(s):  
Membrane Protein ◽  
Secretory Pathway ◽  
Integral Membrane Protein ◽  
Type I ◽  
Coat Proteins ◽  
Protein Traffic ◽  
Early Secretory Pathway ◽  
Er Export ◽  
Different Characteristics ◽  
Related Proteins

Lectins of the early secretory pathway are involved in selective transport of newly synthesized glycoproteins from the endoplasmic reticulum (ER) to the ER–Golgi intermediate compartment (ERGIC). The most prominent cycling lectin is the mannose-binding type I membrane protein ERGIC-53 (ERGIC protein of 53 kDa), a marker for the ERGIC, which functions as a cargo receptor to facilitate export of an increasing number of glycoproteins with different characteristics from the ER. Two ERGIC-53-related proteins, VIP36 (vesicular integral membrane protein 36) and a novel ERGIC-53-like protein, ERGL, are also found in the early secretory pathway. ERGL may act as a regulator of ERGIC-53. Studies of ERGIC-53 continue to provide new insights into the organization and dynamics of the early secretory pathway. Analysis of the cycling of ERGIC-53 uncovered a complex interplay of trafficking signals and revealed novel cytoplasmic ER-export motifs that interact with COP-II coat proteins. These motifs are common to type I and polytopic membrane proteins including presenilin 1 and presenilin 2. The results support the notion that protein export from the ER is selective.

Sign in / Sign up

Export Citation Format

Share Document