scholarly journals A minimal self-organisation model of the Golgi apparatus

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Quentin Vagne ◽  
Jean-Patrick Vrel ◽  
Pierre Sens

The design principles dictating the spatio-temporal organisation of eukaryotic cells, and in particular the mechanisms controlling the self-organisation and dynamics of membrane-bound organelles such as the Golgi apparatus, remain elusive. Although this organelle was discovered 120 years ago, such basic questions as whether vesicular transport through the Golgi occurs in an anterograde (from entry to exit) or retrograde fashion are still strongly debated. Here, we address these issues by studying a quantitative model of organelle dynamics that includes: de-novo compartment generation, inter-compartment vesicular exchange, and biochemical conversion of membrane components. We show that anterograde or retrograde vesicular transports are asymptotic behaviors of a much richer dynamical system. Indeed, the structure and composition of cellular compartments and the directionality of vesicular exchange are intimately linked. They are emergent properties that can be tuned by varying the relative rates of vesicle budding, fusion and biochemical conversion.

2019 ◽  
Author(s):  
Quentin Vagne ◽  
Jean-Patrick Vrel ◽  
Pierre Sens

AbstractThe design principles dictating the spatio-temporal organisation of eukaryotic cells, and in particular the mechanisms controlling the self-organisation and dynamics of membrane-bound organelles such as the Golgi apparatus, remain elusive. Although this organelle was discovered 120 years ago, such basic questions as whether vesicular transport through the Golgi occurs in an anterograde (from entry to exit) or retrograde fashion are still strongly debated. Here, we address these issues by studying a quantitative model of organelle dynamics that includes: de-novo compartment generation, inter-compartment vesicular exchange, and biochemical conversion of membrane components. We show that anterograde or retrograde vesicular transports are asymptotic behaviors of a much richer dynamical system. Indeed, the structure and composition of cellular compartments and the directionality of vesicular exchange are intimately linked. They are emergent properties that can be tuned by varying the relative rates of vesicle budding, fusion and biochemical conversion.


2016 ◽  
Author(s):  
Kristina Sakers ◽  
Allison M. Lake ◽  
Rohan Khazanchi ◽  
Rebecca Ouwenga ◽  
Michael J. Vasek ◽  
...  

AbstractLocal translation in neuronal processes is key to the alteration of synaptic strength that contributes to long term potentiation and learning and memory. Here, we present evidence that astrocytes have ribosomes in their peripheral and perisynaptic processes, and that de novo protein synthesis occurs in the astrocyte periphery. We also developed a new biochemical approach to profile and define a set of candidate transcripts that are locally translated in astrocyte processes, several of which were validated in vivo using in situ hybridization of sparsely labeled cells. Computational analyses indicate that localized translation is both sequence dependent and enriched for particular biological functions. This includes novel pathways such as fatty acid synthesis as well as pathways consistent with known roles for astrocyte processes, such as GABA and glutamate metabolism. Finally, enriched transcripts also include key glial regulators of synaptic refinement, suggesting that local production of astrocyte proteins may support microscale alterations of adjacent synapses.Significance StatementCellular compartments are specialized for particular functions. In astrocytes, the peripheral processes, particularly near synapses, contain proteins specialized for reuptake of neurotransmitters and ions, and have been shown to alter their morphology in response to activity. Regulated transport of a specific subset of nuclear-derived mRNAs to particular compartments is thought to support the specialization of these compartments and allow for local regulation of translation. In neurons, local translation near activated synapses is thought to generate the proteins needed for the synaptic alterations that constitute memory. We demonstrate that astrocytes also have sequence-dependent local translation in their peripheral processes, including transcripts with roles in regulating synapses. This suggests local translation in astrocyte processes may also play a role in modulating synapses.


2019 ◽  
Vol 71 (6) ◽  
pp. 1870-1884 ◽  
Author(s):  
Natalie S Betts ◽  
Christoph Dockter ◽  
Oliver Berkowitz ◽  
Helen M Collins ◽  
Michelle Hooi ◽  
...  

Abstract Mobilization of reserves in germinated cereal grains is critical for early seedling vigour, global crop productivity, and hence food security. Gibberellins (GAs) are central to this process. We have developed a spatio-temporal model that describes the multifaceted mechanisms of GA regulation in germinated barley grain. The model was generated using RNA sequencing transcript data from tissues dissected from intact, germinated grain, which closely match measurements of GA hormones and their metabolites in those tissues. The data show that successful grain germination is underpinned by high concentrations of GA precursors in ungerminated grain, the use of independent metabolic pathways for the synthesis of several bioactive GAs during germination, and a capacity to abort bioactive GA biosynthesis. The most abundant bioactive form is GA1, which is synthesized in the scutellum as a glycosyl conjugate that diffuses to the aleurone, where it stimulates de novo synthesis of a GA3 conjugate and GA4. Synthesis of bioactive GAs in the aleurone provides a mechanism that ensures the hormonal signal is relayed from the scutellum to the distal tip of the grain. The transcript data set of 33 421 genes used to define GA metabolism is available as a resource to analyse other physiological processes in germinated grain.


2003 ◽  
Vol 14 (12) ◽  
pp. 5011-5018 ◽  
Author(s):  
Sapna Puri ◽  
Adam D. Linstedt

It is unclear whether the mammalian Golgi apparatus can form de novo from the ER or whether it requires a preassembled Golgi matrix. As a test, we assayed Golgi reassembly after forced redistribution of Golgi matrix proteins into the ER. Two conditions were used. In one, ER redistribution was achieved using a combination of brefeldin A (BFA) to cause Golgi collapse and H89 to block ER export. Unlike brefeldin A alone, which leaves matrix proteins in relatively large remnant structures outside the ER, the addition of H89 to BFA-treated cells caused ER accumulation of all Golgi markers tested. In the other, clofibrate treatment induced ER redistribution of matrix and nonmatrix proteins. Significantly, Golgi reassembly after either treatment was robust, implying that the Golgi has the capacity to form de novo from the ER. Furthermore, matrix proteins reemerged from the ER with faster ER exit rates. This, together with the sensitivity of BFA remnants to ER export blockade, suggests that presence of matrix proteins in BFA remnants is due to cycling via the ER and preferential ER export rather than their stable assembly in a matrix outside the ER. In summary, the Golgi apparatus appears capable of efficient self-assembly.


1998 ◽  
Vol 333 (3) ◽  
pp. 779-786 ◽  
Author(s):  
Jan Willem KOK ◽  
Teresa BABIA ◽  
Karin KLAPPE ◽  
Gustavo EGEA ◽  
Dick HOEKSTRA

Ceramide (Cer) transfer from the endoplasmic reticulum (ER) to the Golgi apparatus was measured under conditions that block vesicle-mediated protein transfer. This was done either in intact cells by reducing the incubation temperature to 15 °C, or in streptolysin O-permeabilized cells by manipulating the intracellular environment. In both cases, Cer transfer was not inhibited, as demonstrated by the biosynthesis of ceramide monohexosides and sphingomyelin (SM) de novo from metabolically (with [14C]serine) labelled Cer. This assay is based on the knowledge that Cer is synthesized, starting from serine and palmitoyl-CoA, at the ER, whereas glycosphingolipids and SM are synthesized in the (early) Golgi apparatus. Formation of [14C]glycosphingolipids and [14C]SM was observed under conditions that block vesicle-mediated vesicular stomatitis virus glycoprotein transport. These results indicate that [14C]Cer is transferred from ER to Golgi by a non-vesicular mechanism.


2021 ◽  
Author(s):  
G. Ozan Bozdag ◽  
Seyed Alireza Zamani-Dahaj ◽  
Penelope C. Kahn ◽  
Thomas C. Day ◽  
Kai Tong ◽  
...  

The evolution of large organismal size is fundamentally important for multicellularity, creating new ecological niches and opportunities for the evolution of increased biological complexity. Yet little is known about how large size evolves, particularly in nascent multicellular organisms that lack genetically-regulated multicellular development. Here we examine the interplay between biological and biophysical drivers of macroscopic multicellularity using long-term experimental evolution. Over 600 daily transfers (~3,000 generations), multicellular snowflake yeast evolved macroscopic size, becoming ~2·104 times larger (~mm scale) and 104-fold more biophysically tough, while remaining clonal. They accomplished this through sustained biophysical adaptation, evolving increasingly elongate cells that initially reduced the strain of cellular packing, then facilitated branch entanglement so that groups of cells stay together even after many cellular bonds fracture. Four out of five replicate populations show evidence of predominantly adaptive evolution, with mutations becoming significantly enriched in genes affecting cell shape and cell-cell bonds. Taken together, this work shows how selection acting on the emergent properties of simple multicellular groups can drive sustained biophysical adaptation, an early step in the evolution of increasingly complex multicellular organisms.


2003 ◽  
Vol 25 (3) ◽  
pp. 31-33
Author(s):  
John Lucocq

When I was a lad, the adage that “cells are not simply bags full of enzymes” was already popular in biology, and how true it turned out to be. We now know that eukaryotes comprise cellular compartments whose integrity and composition is maintained by specific mechanisms, including the membrane traffic between membrane-bound organelles. So what attracts cell biologists to the challenge of membrane traffic? One reason may be the complexity in composition and spatio-temporal dynamics -- a complexity that manifests itself in the sheer beauty of the physical forms of the trafficking organelles. Another motivation may be the simple question of how complex mixtures of substances can be moved around selectively in membrane-bound vesicles while maintaining the compositional integrity of organelles. Whatever the attraction, it is clear that the full molecular inventory of traffic machinery will be known soon, and we stand now on the threshold of a deeper understanding. It is therefore a good time to look at what has been achieved so far. Interestingly, the focus of membrane trafficking research has come full circle. Initially, discrete organelles with specialized functions were described and then came a mass of molecular information. Now, we are back to the organelles, trying to work out how they are built and how they function in a dynamic way. As in any story of science, the road to discovery has been crucially dependent on clever insights, married with technical developments at both molecular and atomic resolution.


Genes ◽  
2020 ◽  
Vol 11 (5) ◽  
pp. 535
Author(s):  
Yujin Kim ◽  
Joon-Yong An

Transcriptional regulation of the genome arguably provides the basis for the anatomical elaboration and dynamic operation of the human brain. It logically follows that genetic variations affecting gene transcription contribute to mental health disorders, including autism spectrum disorder (ASD). A number of recent studies have shown the role of de novo variants (DNVs) in disrupting early neurodevelopment. However, there is limited knowledge concerning the role of inherited variants during the early brain development of ASD. In this study, we investigate the role of rare inherited variations in neurodevelopment. We conducted co-expression network analyses using an anatomically comprehensive atlas of the developing human brain and examined whether rare coding and regulatory variants, identified from our genetic screening of Australian families with ASD, work in different spatio-temporal functions.


Author(s):  
Nobuko Kawaguchi ◽  
Eleni Nicodemou-Lena ◽  
Kazuhiro Toriyama ◽  
Shuhei Torii ◽  
Yasuo Kitagawa

2021 ◽  
Author(s):  
Chi-Yun Lin ◽  
Matthew Romei ◽  
Irimpan Mathews ◽  
Steven Boxer

The last decades have witnessed an explosion of de novo protein designs with a remarkable range of scaffolds. It remains challenging, however, to design catalytic functions that are competitive with naturally occurring counterparts as well as biomimetic or non-biological catalysts. Although directed evolution often offers efficient solutions, the fitness landscape remains opaque. Green fluorescent protein (GFP), which has revolutionized biological imaging and assays, is one of the most re-designed proteins. While not an enzyme in the conventional sense, GFPs feature competing excited-state decay pathways with the same steric and electrostatic origins as conventional ground-state catalysts, and they exert exquisite control over multiple reaction outcomes through the same principles. Thus, GFP is an “excited-state enzyme”. Herein we show that rationally designed mutants and hybrids that contain environmental mutations and substituted chromophores provide the basis for a quantitative model and prediction that describes the influence of sterics and electrostatics on excited-state catalysis of GFPs. As both perturbations can selectively bias photoisomerization pathways, GFPs with fluorescence quantum yields (FQYs) and photoswitching characteristics tailored for specific applications could be predicted and then demonstrated. The underlying energetic landscape, readily accessible via spectroscopy for GFPs, offers an important missing link in the design of protein function that is generalizable to catalyst design.


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