Special Issue "25 Years of Proteomics in Cell Biology"

A special issue of Cells (ISSN 2073-4409).

Deadline for manuscript submissions: closed (30 September 2019) | Viewed by 20197

Special Issue Editors

Prof. Dr. Hassan Dihazi
E-Mail Website1 Website2
Guest Editor
1. Department of Nephrology and Rheumatology, Göttingen University Medical Center, Georg August University, Göttingen, Germany
2. Centre for Biostructural Imaging of Neurodegeneration (BIN), University Medical Center, Georg August University, Göttingen, Germany
Interests: understanding the pathomechanisms of kidney diseases; investigating therapeutic targets for kidney fibrosis; ER stress proteins and UPR in kidney fibrosis; biomarker discovery and validation
Special Issues, Collections and Topics in MDPI journals
PD Dr. Olaf Jahn
E-Mail Website
Guest Editor
Proteomics Group, Max Planck Institute of Experimental Medicine, Göttingen, Germany
Interests: myelin proteomics; synaptic protein networks; biomarkers of neurological and neuropsychatric diseases; proteomics automation (OJ)

Special Issue Information

Dear Colleagues,

The concept of the proteome is now 25 years old, with Marc Wilkins having coined the term at the first Siena 2D Electrophoresis Meeting in Italy in 1994. We felt that this anniversary is a good time to reflect on what proteomics has achieved in the life sciences in general and in cell biology in particular. In the last 25 years, proteomics has advanced to one of the main pillars in biomedical research and its rapid technological progress was a driving force in many scientific breakthroughs. This Special Issue of Cells will follow the milestones of the development of proteomics and its impact on cell biology during this period, and we are soliciting manuscripts on topics that have had, are having, or will have a formative influence on the field.

Using the title of the 1994 Siena Meeting “2D electrophoresis: from protein maps to genomes” as a point of departure, we would like to cover how 2D electrophoresis has developed from the initial tool for proteome mapping toward a dedicated top-down approach to resolving proteoforms, and how mass spectrometry (MS)-based techniques are currently co-evolving to address this challenging task. The rapid development of the key technology, MS, is also driving the success of bottom-up approaches, and the recent maturation of label-free protein quantification is of particular interest for this Special Issue. From the cell biological perspective, all these technical achievements have led to comprehensive inventories of the proteomes of organelles and other subcellular structures, and we plan to include articles dealing with such valuable resources for the cell biologist. Moreover, we would also like to highlight the role of proteomics as part of the integrative omics endeavor, to reach the coming era of systems biology and big data. Along similar lines, we seek to build bridges from mouse to man, and plan to illuminate how the proteomic concepts that have already fueled basic research in cell biology for many years and are now about to advance clinical applications and, eventually, the coming of age of precision medicine. We will be seeking a balance between review articles and original scientific reports in order to yield a Special Issue of broad interest for students through to experienced researchers in the field of cell biology.

Prof. Dr. Hassan Dihazi
PD Dr. Olaf Jahn
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cells is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2200 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • proteome anniversary
  • top-down and bottom-up proteomics
  • two-dimensional gel electrophoresis
  • label-free quantification
  • organellar and sub-cellular proteomes
  • clinical proteomics
  • integrative omics
  • systems biology
  • clinical applications

Published Papers (10 papers)

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Research

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Article
The Secretome Analysis of Activated Human Renal Fibroblasts Revealed Beneficial Effect of the Modulation of the Secreted Peptidyl-Prolyl Cis-Trans Isomerase A in Kidney Fibrosis
Cells 2020, 9(7), 1724; https://doi.org/10.3390/cells9071724 - 18 Jul 2020
Cited by 5 | Viewed by 1110
Abstract
The secretome is an important mediator in the permanent process of reciprocity between cells and their environment. Components of secretome are involved in a large number of physiological mechanisms including differentiation, migration, and extracellular matrix modulation. Alteration in secretome composition may therefore trigger [...] Read more.
The secretome is an important mediator in the permanent process of reciprocity between cells and their environment. Components of secretome are involved in a large number of physiological mechanisms including differentiation, migration, and extracellular matrix modulation. Alteration in secretome composition may therefore trigger cell transformation, inflammation, and diseases. In the kidney, aberrant protein secretion plays a central role in cell activation and transition and in promoting renal fibrosis onset and progression. Using comparative proteomic analyses, we investigated in the present study the impact of cell transition on renal fibroblast cells secretome. Human renal cell lines were stimulated with profibrotic hormones and cytokines, and alterations in secretome were investigated using proteomic approaches. We identified protein signatures specific for the fibrotic phenotype and investigated the impact of modeling secretome proteins on extra cellular matrix accumulation. The secretion of peptidyl-prolyl cis-trans isomerase A (PPIA) was demonstrated to be associated with fibrosis phenotype. We showed that the in-vitro inhibition of PPIA with ciclosporin A (CsA) resulted in downregulation of PPIA and fibronectin (FN1) expression and significantly reduced their secretion. Knockdown studies of PPIA in a three-dimensional (3D) cell culture model significantly impaired the secretion and accumulation of the extracellular matrix (ECM), suggesting a positive therapeutic effect on renal fibrosis progression. Full article
(This article belongs to the Special Issue 25 Years of Proteomics in Cell Biology)
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Article
Probing the Environment of Emerin by Enhanced Ascorbate Peroxidase 2 (APEX2)-Mediated Proximity Labeling
Cells 2020, 9(3), 605; https://doi.org/10.3390/cells9030605 - 03 Mar 2020
Cited by 4 | Viewed by 2147
Abstract
Emerin is one of the best characterized proteins of the inner nuclear membrane, but can also occur at the level of the endoplasmic reticulum. We now use enhanced ascorbate peroxidase 2 (APEX2) to probe the environment of emerin. APEX2 can be used as [...] Read more.
Emerin is one of the best characterized proteins of the inner nuclear membrane, but can also occur at the level of the endoplasmic reticulum. We now use enhanced ascorbate peroxidase 2 (APEX2) to probe the environment of emerin. APEX2 can be used as a genetic tag that produces short-lived yet highly reactive biotin species, allowing the modification of proteins that interact with or are in very close proximity to the tagged protein. Biotinylated proteins can be isolated using immobilized streptavidin and analyzed by mass spectrometry. As an alternative to the standard approach with a genetic fusion of APEX2 to emerin, we also used RAPIDS (rapamycin- and APEX-dependent identification of proteins by SILAC), a method with improved specificity, where the peroxidase interacts with the protein of interest (i.e., emerin) only upon addition of rapamycin to the cells. We compare these different approaches, which, together, identify well-known interaction partners of emerin like lamin A and the lamina associated polypeptide 1 (LAP1), as well as novel proximity partners. Full article
(This article belongs to the Special Issue 25 Years of Proteomics in Cell Biology)
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Article
Proteomic Analysis of Brain Region and Sex-Specific Synaptic Protein Expression in the Adult Mouse Brain
Cells 2020, 9(2), 313; https://doi.org/10.3390/cells9020313 - 28 Jan 2020
Cited by 11 | Viewed by 2810
Abstract
Genetic disruption of synaptic proteins results in a whole variety of human neuropsychiatric disorders including intellectual disability, schizophrenia or autism spectrum disorder (ASD). In a wide range of these so-called synaptopathies a sex bias in prevalence and clinical course has been reported. Using [...] Read more.
Genetic disruption of synaptic proteins results in a whole variety of human neuropsychiatric disorders including intellectual disability, schizophrenia or autism spectrum disorder (ASD). In a wide range of these so-called synaptopathies a sex bias in prevalence and clinical course has been reported. Using an unbiased proteomic approach, we analyzed the proteome at the interaction site of the pre- and postsynaptic compartment, in the prefrontal cortex, hippocampus, striatum and cerebellum of male and female adult C57BL/6J mice. We were able to reveal a specific repertoire of synaptic proteins in different brain areas as it has been implied before. Additionally, we found a region-specific set of novel synaptic proteins differentially expressed between male and female individuals including the strong ASD candidates DDX3X, KMT2C, MYH10 and SET. Being the first comprehensive analysis of brain region-specific synaptic proteomes from male and female mice, our study provides crucial information on sex-specific differences in the molecular anatomy of the synapse. Our efforts should serve as a neurobiological framework to better understand the influence of sex on synapse biology in both health and disease. Full article
(This article belongs to the Special Issue 25 Years of Proteomics in Cell Biology)
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Article
Delineating the Molecular Basis of the Calmodulin–bMunc13-2 Interaction by Cross-Linking/Mass Spectrometry—Evidence for a Novel CaM Binding Motif in bMunc13-2
Cells 2020, 9(1), 136; https://doi.org/10.3390/cells9010136 - 07 Jan 2020
Cited by 7 | Viewed by 1455
Abstract
Exploring the interactions between the Ca2+ binding protein calmodulin (CaM) and its target proteins remains a challenging task. Members of the Munc13 protein family play an essential role in short-term synaptic plasticity, modulated via the interaction with CaM at the presynaptic compartment. [...] Read more.
Exploring the interactions between the Ca2+ binding protein calmodulin (CaM) and its target proteins remains a challenging task. Members of the Munc13 protein family play an essential role in short-term synaptic plasticity, modulated via the interaction with CaM at the presynaptic compartment. In this study, we focus on the bMunc13-2 isoform expressed in the brain, as strong changes in synaptic transmission were observed upon its mutagenesis or deletion. The CaM–bMunc13-2 interaction was previously characterized at the molecular level using short bMunc13-2-derived peptides only, revealing a classical 1–5–10 CaM binding motif. Using larger protein constructs, we have now identified for the first time a novel and unique CaM binding site in bMunc13-2 that contains an N-terminal extension of a classical 1–5–10 CaM binding motif. We characterize this motif using a range of biochemical and biophysical methods and highlight its importance for the CaM–bMunc13-2 interaction. Full article
(This article belongs to the Special Issue 25 Years of Proteomics in Cell Biology)
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Article
yRACK1/Asc1 proxiOMICs—Towards Illuminating Ships Passing in the Night
Cells 2019, 8(11), 1384; https://doi.org/10.3390/cells8111384 - 04 Nov 2019
Cited by 3 | Viewed by 1667
Abstract
Diverse signals and stress factors regulate the activity and homeostasis of ribosomes in all cells. The Saccharomyces cerevisiae protein Asc1/yRACK1 occupies an exposed site at the head region of the 40S ribosomal subunit (hr40S) and represents a central hub for signaling [...] Read more.
Diverse signals and stress factors regulate the activity and homeostasis of ribosomes in all cells. The Saccharomyces cerevisiae protein Asc1/yRACK1 occupies an exposed site at the head region of the 40S ribosomal subunit (hr40S) and represents a central hub for signaling pathways. Asc1 strongly affects protein phosphorylation and is involved in quality control pathways induced by translation elongation arrest. Therefore, it is important to understand the dynamics of protein formations in the Asc1 microenvironment at the hr40S. We made use of the in vivo protein-proximity labeling technique Biotin IDentification (BioID). Unbiased proxiOMICs from two adjacent perspectives identified nucleocytoplasmic shuttling mRNA-binding proteins, the deubiquitinase complex Ubp3-Bre5, as well as the ubiquitin E3 ligase Hel2 as neighbors of Asc1. We observed Asc1-dependency of hr40S localization of mRNA-binding proteins and the Ubp3 co-factor Bre5. Hel2 and Ubp3-Bre5 are described to balance the mono-ubiquitination of Rps3 (uS3) during ribosome quality control. Here, we show that the absence of Asc1 resulted in massive exposure and accessibility of the C-terminal tail of its ribosomal neighbor Rps3 (uS3). Asc1 and some of its direct neighbors together might form a ribosomal decision tree that is tightly connected to close-by signaling modules. Full article
(This article belongs to the Special Issue 25 Years of Proteomics in Cell Biology)
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Article
The Core Proteome of Biofilm-Grown Clinical Pseudomonas aeruginosa Isolates
Cells 2019, 8(10), 1129; https://doi.org/10.3390/cells8101129 - 23 Sep 2019
Cited by 16 | Viewed by 2557
Abstract
Comparative genomics has greatly facilitated the identification of shared as well as unique features among individual cells or tissues, and thus offers the potential to find disease markers. While proteomics is recognized for its potential to generate quantitative maps of protein expression, comparative [...] Read more.
Comparative genomics has greatly facilitated the identification of shared as well as unique features among individual cells or tissues, and thus offers the potential to find disease markers. While proteomics is recognized for its potential to generate quantitative maps of protein expression, comparative proteomics in bacteria has been largely restricted to the comparison of single cell lines or mutant strains. In this study, we used a data independent acquisition (DIA) technique, which enables global protein quantification of large sample cohorts, to record the proteome profiles of overall 27 whole genome sequenced and transcriptionally profiled clinical isolates of the opportunistic pathogen Pseudomonas aeruginosa. Analysis of the proteome profiles across the 27 clinical isolates grown under planktonic and biofilm growth conditions led to the identification of a core biofilm-associated protein profile. Furthermore, we found that protein-to-mRNA ratios between different P. aeruginosa strains are well correlated, indicating conserved patterns of post-transcriptional regulation. Uncovering core regulatory pathways, which drive biofilm formation and associated antibiotic tolerance in bacterial pathogens, promise to give clues to interactions between bacterial species and their environment and could provide useful targets for new clinical interventions to combat biofilm-associated infections. Full article
(This article belongs to the Special Issue 25 Years of Proteomics in Cell Biology)
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Article
Combined Targeted Omic and Functional Assays Identify Phospholipases A2 that Regulate Docking/Priming in Calcium-Triggered Exocytosis
Cells 2019, 8(4), 303; https://doi.org/10.3390/cells8040303 - 02 Apr 2019
Cited by 3 | Viewed by 2058
Abstract
The fundamental molecular mechanism underlying the membrane merger steps of regulated exocytosis is highly conserved across cell types. Although involvement of Phospholipase A2 (PLA2) in regulated exocytosis has long been suggested, its function or that of its metabolites—a lyso-phospholipid and [...] Read more.
The fundamental molecular mechanism underlying the membrane merger steps of regulated exocytosis is highly conserved across cell types. Although involvement of Phospholipase A2 (PLA2) in regulated exocytosis has long been suggested, its function or that of its metabolites—a lyso-phospholipid and a free fatty acid—remain somewhat speculative. Here, using a combined bioinformatics and top-down discovery proteomics approach, coupled with lipidomic analyses, PLA2 were found to be associated with release-ready cortical secretory vesicles (CV) that possess the minimal molecular machinery for docking, Ca2+ sensing and membrane fusion. Tightly coupling the molecular analyses with well-established quantitative fusion assays, we show for the first time that inhibition of a CV surface calcium independent intracellular PLA2 and a luminal secretory PLA2 significantly reduce docking/priming in the late steps of regulated exocytosis, indicating key regulatory roles in the critical step(s) preceding membrane merger. Full article
(This article belongs to the Special Issue 25 Years of Proteomics in Cell Biology)
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Review

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Review
Proteomics of Crystal–Cell Interactions: A Model for Kidney Stone Research
Cells 2019, 8(9), 1076; https://doi.org/10.3390/cells8091076 - 12 Sep 2019
Cited by 26 | Viewed by 2244
Abstract
Nephrolithiasis/urolithiasis (i.e., kidney stone disease) remains a global public health problem with increasing incidence/prevalence. The most common chemical composition of kidney stones is calcium oxalate that initiates stone formation by crystallization, crystal growth, crystal aggregation, crystal–cell adhesion, and crystal invasion through extracellular matrix [...] Read more.
Nephrolithiasis/urolithiasis (i.e., kidney stone disease) remains a global public health problem with increasing incidence/prevalence. The most common chemical composition of kidney stones is calcium oxalate that initiates stone formation by crystallization, crystal growth, crystal aggregation, crystal–cell adhesion, and crystal invasion through extracellular matrix in renal interstitium. Among these processes, crystal–cell interactions (defined as “the phenomena in which the cell is altered by any means of effects from the crystal that adheres onto cellular surface or is internalized into the cell, accompanying with changes of the crystal, e.g., growth, adhesive capability, degradation, etc., induced by the cell”) are very important for crystal retention in the kidney. During the past 12 years, proteomics has been extensively applied to kidney stone research aiming for better understanding of the pathogenic mechanisms of kidney stone formation. This article provides an overview of the current knowledge in this field and summarizes the data obtained from all the studies that applied proteomics to the investigations of crystal–cell interactions that subsequently led to functional studies to address the significant impact or functional roles of the expression proteomics data in the pathogenesis of kidney stone disease. Full article
(This article belongs to the Special Issue 25 Years of Proteomics in Cell Biology)
Review
Proteomics in the World of Induced Pluripotent Stem Cells
Cells 2019, 8(7), 703; https://doi.org/10.3390/cells8070703 - 11 Jul 2019
Cited by 7 | Viewed by 2036
Abstract
Omics approaches have significantly impacted knowledge about molecular signaling pathways driving cell function. Induced pluripotent stem cells (iPSC) have revolutionized the field of biological sciences and proteomics and, in particular, has been instrumental in identifying key elements operating during the maintenance of the [...] Read more.
Omics approaches have significantly impacted knowledge about molecular signaling pathways driving cell function. Induced pluripotent stem cells (iPSC) have revolutionized the field of biological sciences and proteomics and, in particular, has been instrumental in identifying key elements operating during the maintenance of the pluripotent state and the differentiation process to the diverse cell types that form organisms. This review covers the evolution of conceptual and methodological strategies in proteomics; briefly describes the generation of iPSC from a historical perspective, the state-of-the-art of iPSC-based proteomics; and compares data on the proteome and transcriptome of iPSC to that of embryonic stem cells (ESC). Finally, proteomics of healthy and diseased cells and organoids differentiated from iPSC are analyzed. Full article
(This article belongs to the Special Issue 25 Years of Proteomics in Cell Biology)
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Meeting Report
Mapping Cellular Microenvironments: Proximity Labeling and Complexome Profiling (Seventh Symposium of the Göttingen Proteomics Forum)
Cells 2019, 8(10), 1192; https://doi.org/10.3390/cells8101192 - 02 Oct 2019
Cited by 2 | Viewed by 1492
Abstract
Mass spectrometry-based proteomics methods are finding increasing use in structural biology research. Beyond simple interaction networks, information about stable protein-protein complexes or spatially proximal proteins helps to elucidate the biological functions of proteins in a wider cellular context. To shed light on new [...] Read more.
Mass spectrometry-based proteomics methods are finding increasing use in structural biology research. Beyond simple interaction networks, information about stable protein-protein complexes or spatially proximal proteins helps to elucidate the biological functions of proteins in a wider cellular context. To shed light on new developments in this field, the Göttingen Proteomics Forum organized a one-day symposium focused on complexome profiling and proximity labeling, two emerging technologies that are gaining significant attention in biomolecular research. The symposium was held in Göttingen, Germany on 23 May, 2019, as part of a series of regular symposia organized by the Göttingen Proteomics Forum. Full article
(This article belongs to the Special Issue 25 Years of Proteomics in Cell Biology)
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