Browse
Submit Data
Databases
API
Help

Dataset Information

31 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Nonequilibrium description of de novo biogenesis and transport through Golgi-like cisternae.

ABSTRACT: A central issue in cell biology is the physico-chemical basis of organelle biogenesis in intracellular trafficking pathways, its most impressive manifestation being the biogenesis of Golgi cisternae. At a basic level, such morphologically and chemically distinct compartments should arise from an interplay between the molecular transport and chemical maturation. Here, we formulate analytically tractable, minimalist models, that incorporate this interplay between transport and chemical progression in physical space, and explore the conditions for de novo biogenesis of distinct cisternae. We propose new quantitative measures that can discriminate between the various models of transport in a qualitative manner-this includes measures of the dynamics in steady state and the dynamical response to perturbations of the kind amenable to live-cell imaging.

SUBMITTER: Sachdeva H

PROVIDER: S-EPMC5171829 | biostudies-other | 2016 Dec

REPOSITORIES: biostudies-other

ACCESS DATA

Json Xml

Publications

Nonequilibrium description of de novo biogenesis and transport through Golgi-like cisternae.

Sachdeva Himani H Barma Mustansir M Rao Madan M

Scientific reports 20161219

A central issue in cell biology is the physico-chemical basis of organelle biogenesis in intracellular trafficking pathways, its most impressive manifestation being the biogenesis of Golgi cisternae. At a basic level, such morphologically and chemically distinct compartments should arise from an interplay between the molecular transport and chemical maturation. Here, we formulate analytically tractable, minimalist models, that incorporate this interplay between transport and chemical progression ...[more]

PMID: 27991496

Similar Datasets

Biogenesis of tubular ER-to-Golgi transport intermediates.

Project description:Tubular transport intermediates (TTIs) have been described as one class of transport carriers in endoplasmic reticulum (ER)-to-Golgi transport. In contrast to vesicle budding and fusion, little is known about the molecular regulation of TTI synthesis, transport and fusion with target membranes. Here we have used in vivo imaging of various kinds of GFP-tagged proteins to start to address these questions. We demonstrate that under steady-state conditions TTIs represent approximately 20% of all moving transport carriers. They increase in number and length when more transport cargo becomes available at the donor membrane, which we induced by either temperature-related transport blocks or increased expression of the respective GFP-tagged transport markers. The formation and motility of TTIs is strongly dependent on the presence of intact microtubules. Microinjection of GTPgammaS increases the frequency of TTI synthesis and the length of these carriers. When Rab proteins are removed from membranes by microinjection of recombinant Rab-GDI, the synthesis of TTIs is completely blocked. Microinjection of the cytoplasmic tails of the p23 and p24 membrane proteins also abolishes formation of p24-containing TTIs. Our data suggest that TTIs are ER-to-Golgi transport intermediates that form preferentially when transport-competent cargo exists in excess at the donor membrane. We propose a model where the interaction of the cytoplasmic tails of membrane proteins with microtubules are key determinants for TTI synthesis and may also serve as a so far unappreciated model for aspects of transport carrier formation.

| S-EPMC1356583 | biostudies-literature

Acute perturbations in Golgi organization impact de novo sphingomyelin synthesis.

Project description:The mammalian Golgi apparatus is composed of multiple stacks of cisternal membranes organized laterally into a ribbon-like structure, with close apposition of trans Golgi regions with specialized endoplasmic reticulum (ER) membranes. These contacts may be the site of ceramide transfer from its site of synthesis (ER) to sphingomyelin (SM) synthase through ceramide transfer protein (CERT). CERT extracts ceramide from the ER and transfers it to Golgi membranes but the role of overall Golgi structure in this process is unknown. We show here that localization of CERT in puncta around the Golgi complex requires both ER- and Golgi-binding domains of CERT. To examine how Golgi structure contributes to SM synthesis, we treated cells with Golgi-perturbing drugs and measured newly synthesized SM. Interestingly, disruption of Golgi morphology with nocodazole, but not ilimaquinone inhibited SM synthesis. Decreased localization of CERT with a Golgi marker correlated with decreased SM synthesis. We propose that some Golgi structural perturbations interfere with efficient ceramide trafficking through CERT, and thus SM synthesis. The organization of the mammalian Golgi ribbon together with CERT may promote specific ER-Golgi interactions for efficient delivery of ceramide for SM synthesis.

| S-EPMC2862547 | biostudies-literature

Plk4 triggers autonomous de novo centriole biogenesis and maturation.

Project description:Centrioles form centrosomes and cilia. In most proliferating cells, centrioles assemble through canonical duplication, which is spatially, temporally, and numerically regulated by the cell cycle and the presence of mature centrioles. However, in certain cell types, centrioles assemble de novo, yet by poorly understood mechanisms. Herein, we established a controlled system to investigate de novo centriole biogenesis, using Drosophila melanogaster egg explants overexpressing Polo-like kinase 4 (Plk4), a trigger for centriole biogenesis. We show that at a high Plk4 concentration, centrioles form de novo, mature, and duplicate, independently of cell cycle progression and of the presence of other centrioles. Plk4 concentration determines the temporal onset of centriole assembly. Moreover, our results suggest that distinct biochemical kinetics regulate de novo and canonical biogenesis. Finally, we investigated which other factors modulate de novo centriole assembly and found that proteins of the pericentriolar material (PCM), and in particular γ-tubulin, promote biogenesis, likely by locally concentrating critical components.

| S-EPMC7995200 | biostudies-literature

The intraflagellar transport protein IFT20 controls lysosome biogenesis by regulating the post-Golgi transport of acid hydrolases.

Project description:The assembly and function of the primary cilium depends on multimolecular intraflagellar transport (IFT) complexes that shuttle their cargo along the axonemal microtubules through their interaction with molecular motors. The IFT system has been moreover recently implicated in a reciprocal interplay between autophagy and ciliogenesis. We have previously reported that IFT20 and other components of the IFT complexes participate in the assembly of the immune synapse in the non-ciliated T cell, suggesting that other cellular processes regulated by the IFT system in ciliated cells, including autophagy, may be shared by cells lacking a cilium. Starting from the observation of a defect in autophagic clearance and an accumulation of lipid droplets in IFT20-deficient T cells, we show that IFT20 is required for lysosome biogenesis and function by controlling the lysosomal targeting of acid hydrolases. This function involves its ability to regulate the retrograde traffic of the cation-independent mannose-6-phosphate receptor (CI-MPR) to the trans-Golgi network, which is achieved by coupling recycling CI-MPRs to the microtubule motor dynein. Consistent with the lysosomal defect, an upregulation of the TFEB-dependent expression of the lysosomal gene network can be observed in IFT20-deficient cells, which is associated with defective tonic T-cell antigen receptor signaling and mTOR activity. We additionally show that the lysosome-related function of IFT20 extends to non-ciliated cells other than T cells, as well as to ciliated cells. Our findings provide the first evidence that a component of the IFT system that controls ciliogenesis is implicated in the biogenesis of lysosomes.

| S-EPMC7205998 | biostudies-literature

Atg2: A novel phospholipid transfer protein that mediates de novo autophagosome biogenesis.

Project description:The degradation of cytoplasmic components via autophagy is crucial for intracellular homeostasis. In the process of autophagy, a newly synthesized isolation membrane (IM) is developed to sequester degradation targets and eventually the IM seals, forming an autophagosome. One of the most poorly understood autophagy-related proteins is Atg2, which is known to localize to a contact site between the edge of the expanding IM and the exit site of the endoplasmic reticulum (ERES). Recent advances in structural and biochemical analyses have been applied to Atg2 and have revealed it to be a novel multifunctional protein that tethers membranes and transfers phospholipids between them. Considering that Atg2 is essential for the expansion of the IM that requires phospholipids as building blocks, it is suggested that Atg2 transfers phospholipids from the ERES to the IM during the process of autophagosome formation, suggesting that lipid transfer proteins can mediate de novo organelle biogenesis.

| S-EPMC6511744 | biostudies-literature

MON2 Guides Wntless Transport to the Golgi through Recycling Endosomes.

Project description:Endocytic cargos are transported to recycling endosomes (RE) but how these sorting platforms are generated is not well understood. Here we describe our biochemical and live imaging studies of the conserved MON2-DOPEY complex in RE formation. MON2 mainly co-localized with RE marker RAB4B in peripheral dots and perinuclear region. The peripheral RE approached, interacted with, and separated from sorting nexin 3 (SNX3)-positive early endosomes (EE). Membrane-bound DOPEY2 was recruited to RE dependent upon MON2 expression, and showed binding abilities to kinesin and dynein/dynactin motor proteins. MON2-knockout impaired segregation of RE from EE and led to a decreased tubular recycling endosomal network, whereas RE was accumulated at perinuclear regions in DOPEY2-knockout cells. MON2 depletion also impaired intracellular transferrin receptor recycling, as well as retrograde transport of Wntless during its passage through RE before delivery from EE to the Golgi. Together, these data suggest that the MON2 drives separation of RE from EE and is required for efficient transport of endocytic cargo molecules.Key words: membrane trafficking, MON2, recycling endosomes, Wntless.

| S-EPMC10511057 | biostudies-literature

Molecular de-novo design through deep reinforcement learning.

Project description:This work introduces a method to tune a sequence-based generative model for molecular de novo design that through augmented episodic likelihood can learn to generate structures with certain specified desirable properties. We demonstrate how this model can execute a range of tasks such as generating analogues to a query structure and generating compounds predicted to be active against a biological target. As a proof of principle, the model is first trained to generate molecules that do not contain sulphur. As a second example, the model is trained to generate analogues to the drug Celecoxib, a technique that could be used for scaffold hopping or library expansion starting from a single molecule. Finally, when tuning the model towards generating compounds predicted to be active against the dopamine receptor type 2, the model generates structures of which more than 95% are predicted to be active, including experimentally confirmed actives that have not been included in either the generative model nor the activity prediction model. Graphical abstract .

| S-EPMC5583141 | biostudies-literature

Human megakaryocytic microparticles induce de novo platelet biogenesis in a wild-type murine model.

Project description:Platelet transfusions are used to treat idiopathic or drug-induced thrombocytopenia. Platelets are an expensive product in limited supply, with limited storage and distribution capabilities because they cannot be frozen. We have demonstrated that, in vitro, human megakaryocytic microparticles (huMkMPs) target human CD34+ hematopoietic stem and progenitor cells (huHSPCs) and induce their Mk differentiation and platelet biogenesis in the absence of thrombopoietin. In this study, we showed that, in vitro, huMkMPs can also target murine HSPCs (muHSPCs) to induce them to differentiate into megakaryocytes in the absence of thrombopoietin. Based on that, using wild-type BALB/c mice, we demonstrated that intravenously administering 2 × 106 huMkMPs triggered de novo murine platelet biogenesis to increase platelet levels up to 49% 16 hours after administration. huMkMPs also largely rescued low platelet levels in mice with induced thrombocytopenia 16 hours after administration by increasing platelet counts by 51%, compared with platelet counts in thrombocytopenic mice. Normalized on a tissue-mass basis, biodistribution experiments show that MkMPs localized largely to the bone marrow, lungs, and liver 24 hours after huMkMP administration. Beyond the bone marrow, CD41+ (megakaryocytes and Mk-progenitor) cells were frequent in lungs, spleen, and especially, liver. In the liver, infused huMKMPs colocalized with Mk progenitors and muHSPCs, thus suggesting that huMkMPs interact with muHSPCs in vivo to induce platelet biogenesis. Our data demonstrate the potential of huMkMPs, which can be stored frozen, to treat thrombocytopenias and serve as effective carriers for in vivo, target-specific cargo delivery to HSPCs.

| S-EPMC7065487 | biostudies-literature

Tricalbins Are Required for Non-vesicular Ceramide Transport at ER-Golgi Contacts and Modulate Lipid Droplet Biogenesis.

Project description:Lipid composition varies among organelles, and the distinct lipid composition is important for specific functions of each membrane. Lipid transport between organelles, which is critical for the maintenance of membrane lipid composition, occurs by either vesicular or non-vesicular mechanisms. In yeast, ceramide synthesized in the endoplasmic reticulum (ER) is transported to the Golgi apparatus where inositolphosphorylceramide (IPC) is formed. Here we show that a fraction of Tcb3p, a yeast tricalbin protein, localizes to ER-Golgi contact sites. Tcb3p and their homologs Tcb1p and Tcb2p are required for formation of ER-Golgi contacts and non-vesicular ceramide transport. Absence of Tcb1p, Tcb2p, and Tcb3p increases acylceramide synthesis and subsequent lipid droplet (LD) formation. As LD can sequester excess lipids, we propose that tricalbins act as regulators of ceramide transport at ER-Golgi contact sites to help reduce a potentially toxic accumulation of ceramides.

| S-EPMC7648140 | biostudies-literature

Plant gene editing through de novo induction of meristems.

Project description:Plant gene editing is typically performed by delivering reagents such as Cas9 and single guide RNAs to explants in culture. Edited cells are then induced to differentiate into whole plants by exposure to various hormones. The creation of edited plants through tissue culture is often inefficient, time-consuming, works for only limited species and genotypes, and causes unintended changes to the genome and epigenome. Here we report two methods to generate gene-edited dicotyledonous plants through de novo meristem induction. Developmental regulators and gene-editing reagents are delivered to somatic cells of whole plants. This induces meristems that produce shoots with targeted DNA modifications, and gene edits are transmitted to the next generation. The de novo induction of gene-edited meristems sidesteps the need for tissue culture and promises to overcome a bottleneck in plant gene editing.

| S-EPMC6954279 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data