Spatial proteomics of vesicular trafficking: coupling mass spectrometry and imaging approaches in membrane biology

Zhang, Liang; Liang, Xinlin; Takáč, Tomáš; Komis, George; Li, Xiaojuan; Zhang, Yuan; Ovečka, Miroslav; Chen, Yanmei; Šamaj, Jozef

doi:10.1111/pbi.13929

Cited by 15 publications

(8 citation statements)

References 156 publications

(192 reference statements)

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“…Rabs, small GTPases that play an essential role in intracellular vesicular transport, serve as key switches that regulate membrane transport within eukaryotic cells. Rab proteins interact with their binding domain (RBD) to recruit Rab effectors into subcellular compartments via their binding domain, regulating vesicle formation, transport, and fusion processes [114][115][116]. Leucine-rich repeat kinase 2 (LRRK2) can directly phosphorylate Rabs; when overexpressed, 14 Rabs become substrates of endogenous LRRK2.…”

Section: Golgi Apparatus-parkinsonmentioning

confidence: 99%

The Golgi Apparatus: A Voyage through Time, Structure, Function and Implication in Neurodegenerative Disorders

Mohan,

Calenic,

Ghiurau

et al. 2023

Cells

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This comprehensive review article dives deep into the Golgi apparatus, an essential organelle in cellular biology. Beginning with its discovery during the 19th century until today’s recognition as an important contributor to cell function. We explore its unique organization and structure as well as its roles in protein processing, sorting, and lipid biogenesis, which play key roles in maintaining homeostasis in cellular biology. This article further explores Golgi biogenesis, exploring its intricate processes and dynamics that contribute to its formation and function. One key focus is its role in neurodegenerative diseases like Parkinson’s, where changes to the structure or function of the Golgi apparatus may lead to their onset or progression, emphasizing its key importance in neuronal health. At the same time, we examine the intriguing relationship between Golgi stress and endoplasmic reticulum (ER) stress, providing insights into their interplay as two major cellular stress response pathways. Such interdependence provides a greater understanding of cellular reactions to protein misfolding and accumulation, hallmark features of many neurodegenerative diseases. In summary, this review offers an exhaustive examination of the Golgi apparatus, from its historical background to its role in health and disease. Additionally, this examination emphasizes the necessity of further research in this field in order to develop targeted therapeutic approaches for Golgi dysfunction-associated conditions. Furthermore, its exploration is an example of scientific progress while simultaneously offering hope for developing innovative treatments for neurodegenerative disorders.

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Section: Golgi Apparatus-parkinsonmentioning

confidence: 99%

The Golgi Apparatus: A Voyage through Time, Structure, Function and Implication in Neurodegenerative Disorders

Mohan,

Calenic,

Ghiurau

et al. 2023

Cells

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“…Recent developments in mass spectrometry imaging (MSI) enable spatial mapping of the relative distribution and abundances of proteins, peptides, lipids, small molecule metabolites, drugs and elemental isotopes in heterogeneous tissue sections 1 with resolution at, or near, cellular 2 . Hence, MSI has become a promising tool in the era of spatial-omics [3][4][5][6][7][8][9][10][11][12][13][14][15] , especially at the single cell level 16 . Matrixassisted laser desorption and ionization (MALDI) and desorption electrospray ionization (DESI) are the dominant modes of ionization for MSI.…”

Section: Introductionmentioning

confidence: 99%

Untargeted Pixel-by-Pixel Imaging of Metabolite Ratio Pairs as a Novel Tool for Biomedical Discovery in Mass Spectrometry Imaging

Cheng,

Miller,

Southwell

et al. 2024

Preprint

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Mass spectrometry imaging (MSI) is a powerful technology that can be employed to define the spatial distribution and relative abundance of structurally identified and yet-undefined metabolites across a tissue cryosection. While numerous software packages enable pixel-by-pixel imaging of individual metabolite distributions, the research community lacks a discovery tool that provides spatial imaging of all metabolite abundance ratio pairs. Importantly, the recognition of correlating metabolite pairs offers a strategy to discover unanticipated molecules that contribute to or regulate a shared metabolic pathway, uncover hidden metabolic heterogeneity across cells and tissue subregions, and offers a single timepoint indicator of flux through a particular metabolic pathway of interest. Here, we describe the development and implementation of an untargeted R package workflow for pixel-by-pixel imaging of ratios for all metabolites detected in an MSI experiment. Considering untargeted MSI studies of murine brain and embryogenesis, we demonstrate that ratio imaging offers the opportunity to minimize systematic data variation introduced during sample handling or due to instrument drift, markedly enhances spatial image resolution, and can serve to reveal previously unrecognized tissue regions that are metabotype-distinct. Furthermore, ratio imaging facilitates the discovery of novel regional biomarkers, and can provide anatomical information regarding the spatial distribution of metabolite-linked biochemical pathways. The algorithm described herein is generic and can be applied to any MSI dataset containing spatial information for metabolites, peptides or proteins. Importantly, this software package offers a powerful add-on tool that can significantly enhance knowledge obtained from currently employed spatial metabolite profiling technologies.

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“…The Rab binds with Rab effectors through binding domain (RBD) and recruits effectors to subcellular compartments to exert their effects. Effectors are used to regulate vesicle formation, transport and fusion by using other domains ( Waschbusch et al, 2021 ; Zhang et al, 2022 ).…”

Section: Introductionmentioning

confidence: 99%

The function of Golgi apparatus in LRRK2-associated Parkinson’s disease

Wei

Awan²,

Bai³

et al. 2023

Front. Mol. Neurosci.

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Parkinson’s disease (PD) is a chronic neurodegenerative disease associated with the intracellular organelles. Leucine-rich repeat kinase 2 (LRRK2) is a large multi-structural domain protein, and mutation in LRRK2 is associated with PD. LRRK2 regulates intracellular vesicle transport and function of organelles, including Golgi and lysosome. LRRK2 phosphorylates a group of Rab GTPases, including Rab29, Rab8, and Rab10. Rab29 acts in a common pathway with LRRK2. Rab29 has been shown to recruit LRRK2 to the Golgi complex (GC) to stimulate LRRK2 activity and alter the Golgi apparatus (GA). Interaction between LRRK2 and Vacuolar protein sorting protein 52 (VPS52), a subunit of the Golgi-associated retrograde protein (GARP) complex, mediates the function of intracellular soma trans-Golgi network (TGN) transport. VPS52 also interacts with Rab29. Knockdown of VPS52 leads to the loss of LRRK2/Rab29 transported to the TGN. Rab29, LRRK2, and VPS52 work together to regulate functions of the GA, which is associated with PD. We highlight recent advances in the roles of LRRK2, Rabs, VPS52, and other molecules, such as Cyclin-dependent kinase 5 (CDK5) and protein kinase C (PKC) in the GA, and discuss their possible association with the pathological mechanisms of PD.

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Spatial proteomics of vesicular trafficking: coupling mass spectrometry and imaging approaches in membrane biology

Cited by 15 publications

References 156 publications

The Golgi Apparatus: A Voyage through Time, Structure, Function and Implication in Neurodegenerative Disorders

The Golgi Apparatus: A Voyage through Time, Structure, Function and Implication in Neurodegenerative Disorders

Untargeted Pixel-by-Pixel Imaging of Metabolite Ratio Pairs as a Novel Tool for Biomedical Discovery in Mass Spectrometry Imaging

The function of Golgi apparatus in LRRK2-associated Parkinson’s disease

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