Dataset Information

PDZD8 interacts with Protrudin and Rab7 to form an ER-late endosome membrane contact site that recruits mitochondria

ABSTRACT: Endosomes regulate a plethora of cellular processes including signaling, nutrient status and organelle quality control by controlling the fate of material entering the cells. Endosomes undergo a process of maturation which specifies whether material will be shuttled back to the cell surface or degraded by the lysosome. Nevertheless, a complete inventory of factors regulating endosomal maturation is still lacking. Recently, membrane contact sites (MCSs) between the endoplasmic reticulum (ER) and endosomes have emerged as important players in endosomal sorting, dynamics and motility. Here, we identify the ER transmembrane protein PDZD8 as a new Rab7 effector that, together with the MCS component Protrudin, forms an ER-late endosome MCS. At these ER-late endosome MCSs, PDZD8 also recruits mitochondria to form a three-way contact. Our data suggest that the PDZD8/Protrudin-Rab7 MCS functions to facilitate an early stage of late endosome maturation.

INSTRUMENT(S): Q Exactive Plus

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Epithelial Cell, Colon

DISEASE(S): Colon Cancer

SUBMITTER: Tamar Geiger

LAB HEAD: Tamar Geiger

PROVIDER: PXD015523 | Pride | 2020-06-02

REPOSITORIES: Pride

ACCESS DATA

Dataset's files

Source:

			Action	DRS
	Animal_20170714_MH_SA_Yael_1.raw	Raw
	Animal_20170714_MH_SA_Yael_10.raw	Raw
	Animal_20170714_MH_SA_Yael_11.raw	Raw
	Animal_20170714_MH_SA_Yael_12.raw	Raw
	Animal_20170714_MH_SA_Yael_13.raw	Raw

Items per page:

1 - 5 of 25

Publications

PDZD8 interacts with Protrudin and Rab7 at ER-late endosome membrane contact sites associated with mitochondria.

Elbaz-Alon Yael Y Guo Yuting Y Segev Nadav N Harel Michal M Quinnell Daniel E DE Geiger Tamar T Avinoam Ori O Li Dong D Nunnari Jodi J

Nature communications 20200720 1

Endosomes are compositionally dynamic organelles that regulate signaling, nutrient status and organelle quality by specifying whether material entering the cells will be shuttled back to the cell surface or degraded by the lysosome. Recently, membrane contact sites (MCSs) between the endoplasmic reticulum (ER) and endosomes have emerged as important players in endosomal protein sorting, dynamics and motility. Here, we show that PDZD8, a Synaptotagmin-like Mitochondrial lipid-binding Proteins (SM ...[more]

PMID: 32686675

Similar Datasets

Project description:Cut-out switch model Membrane identity and GTPase cascades regulated by toggle and cut-out switches Perla Del Conte-Zerial, Lutz Brusch, Jochen C Rink, Claudio Collinet, Yannis Kalaidzidis, Marino Zerial, and Andreas Deutsch: Molecular Systems Biology4:206 15 July 2008, doi:10.1038/msb.2008.45 This is the cut-out switch model for the Rab5 - Rab7 transition, also referred to as model 2 in the original publication. This model is not completely described in all details in the publication. Thanks go to Barbara Szomolay and Lutz Brusch for finding and clarifying this. According to Dr. Brusch this model represents the mechanism identified by the qualitative analysis in the article in the scenario deemed most useful by the authors. For the time-course simulations it was necessary to add a time dependency to one of the parameters, which is only verbally described in the article. As argued in the publication the switch between early and late endosomes can be triggered by a parameter change. While with fixed parameter values each switch just converges to one steady state from its initial conditions and stays there, endosomes should switch between two different states. These changes would in reality of course depend on many different factors, such as cargo composition and amount in the specific endosome, its location and some additional cellular control mechanisms and encompass many different parameters. To keep the model simple the authors chose to add a time dependency to only one reaction - ke in the activation of RAB5 is multiplied with a term monotonously increasing over time from 0 to 1. They also hard coded a time dependence in this term, 100 minutes, to make the switch occur after several hundred minutes. As long as this modulating term remains monotonic all resulting time courses should look similar, with the switching behavior depending on the initial conditions and whether the term is increasing or decreasing. Monotonic increase is a reasonable assumption for the described mechanism of cargo accumulation. Not explicitly described in the article: activation of Rab5 (time) : r*ke*time/(100+time) /(1+e(kg-R)*kf) instead of r*ke/(1+e(kg-R)*kf) This model originates from BioModels Database: A Database of Annotated Published Models. It is copyright (c) 2005-2009 The BioModels Team.For more information see the terms of use.To cite BioModels Database, please use Le Novère N., Bornstein B., Broicher A., Courtot M., Donizelli M., Dharuri H., Li L., Sauro H., Schilstra M., Shapiro B., Snoep J.L., Hucka M. (2006) BioModels Database: A Free, Centralized Database of Curated, Published, Quantitative Kinetic Models of Biochemical and Cellular Systems Nucleic Acids Res., 34: D689-D691.

Project description:Neurons require efficient transport mechanisms such as fast axonal transport to ensure neuronal homeostasis and survival. Neurotrophins and their receptors are conveyed via fast axonal retrograde transport of signaling endosomes to the soma, where they elicit transcriptional responses. Despite the essential roles of signaling endosomes in neuronal differentiation and survival, little is known about their molecular identity, dynamics and regulation. Gaining a better mechanistic understanding of these organelles and their kinetics is crucial, given the growing evidence linking vesicular trafficking deficits to neurodegeneration. Here, we exploited an affinity purification strategy using the binding fragment of tetanus neurotoxin (HCT) conjugated to monocrystalline iron oxide nanoparticles (MIONs), which in motor neurons, is transported in the same carriers as neurotrophins and their receptors. To quantitatively assess the molecular composition of HCT-containing signaling endosomes, we have developed a protocol for triple Stable Isotope Labeling with Amino acids in Cell culture (SILAC) in embryonic stem cell-derived motor neurons. After HCT internalization, retrograde carriers were magnetically isolated at different time points and subjected to mass-spectrometry and gene ontology analyses. This purification strategy is highly specific, as confirmed by the presence of essential regulators of fast axonal transport in the make-up of these organelles. Our results indicate that signaling endosomes undergo a rapid maturation with the acquisition of late endosome markers following a specific time-dependent kinetics. Strikingly, signaling endosomes are specifically enriched in proteins known to be involved in neurodegenerative diseases and neuroinfection. Moreover, we highlighted the presence of novel components, whose precise temporal recruitment on signaling endosomes might be essential for proper sorting and/or transport of these organelles. This study provides the first quantitative proteomic analysis of signaling endosomes isolated from motor neurons and allows the assembly of a functional map of these axonal carriers involved in long-range neuronal signaling.