Glycans in autophagy, endocytosis and lysosomal functions

Reggiori, Fulvio; Gabius, Hans‐Joachim; Aureli, Massimo; Römer, Winfried; Sonnino, Sandro; Eskelinen, Eeva‐Liisa

doi:10.1007/s10719-021-10007-x

Cited by 18 publications

(10 citation statements)

References 273 publications

(307 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Normally, inactive EV cargo biomolecules are internalized efficiently through the endocytosis pathway. [ 118 ] The mechanism underlying sEV uptake by different recipient cells is yet unknown. Further, it is not necessary that all active EV cargo biomolecules have biological function only in the cytoplasm.…”

Section: Perspectives Of Smlm For Sev Imagingmentioning

confidence: 99%

Single Molecule Localization Microscopy for Studying Small Extracellular Vesicles

Ghanam

Chetty

Zhu

et al. 2023

Small

View full text Add to dashboard Cite

guidelines suggests that EV researchers use the term small EVs (sEVs) for vesicles that are less than 200 nm in diameter. [4] sEVs contain many essential cargo biomolecules such as nucleic acids (DNA, mRNA, microRNA), proteins, and lipids. [1,3,5] sEVs have emerged as a functional mediator for communications between cells in health and disease. [1,6] sEVs derived from tumor cells contain disease-specific proteins, RNA, and double-stranded DNA (dsDNA), thereby representing the disease state and progression. [1,2,[7][8][9] Especially in tumor microenvironment, sEVs transfer their cargo from the tumor to stromal cells. [10,11] sEVs play pathophysiological roles in many other diseases, including neurodegenerative diseases, and various infections. They transmit important biomolecules that regulate many biological processes and influence the immune system. [1,[12][13][14][15] In the last decade, studies dealing with sEV biogenesis pathways and the role of sEVs in health and disease have grown exponentially. However, exploring the released sEVs and interaction of their cargo with cellular biomolecules in the distant recipient cells is significantly hampered by the lack of microscopy studies using improved imaging technology. Most of the current microscopy studies involving sEVs use conventional confocal microscopy to generate either 2D or 3D reconstruction images using Imaris. [11,[16][17][18][19][20][21][22] Although these images provide the information Small extracellular vesicles (sEVs) are 30-200 nm nanovesicles enriched with unique cargoes of nucleic acids, lipids, and proteins. sEVs are released by all cell types and have emerged as a critical mediator of cell-to-cell communication. Although many studies have dealt with the role of sEVs in health and disease, the exact mechanism of sEVs biogenesis and uptake remain unexplored due to the lack of suitable imaging technologies. For sEVs functional studies, imaging has long relied on conventional fluorescence microscopy that has only 200-300 nm resolution, thereby generating blurred images. To break this resolution limit, recent developments in super-resolution microscopy techniques, specifically single-molecule localization microscopy (SMLM), expanded the understanding of subcellular details at the few nanometer level. SMLM success relies on the use of appropriate fluorophores with excellent blinking properties. In this review, the basic principle of SMLM is highlighted and the state of the art of SMLM use in sEV biology is summarized. Next, how SMLM techniques implemented for cell imaging can be translated to sEV imaging is discussed by applying different labeling strategies to study sEV biogenesis and their biomolecular interaction with the distant recipient cells.

show abstract

Section: Perspectives Of Smlm For Sev Imagingmentioning

confidence: 99%

Single Molecule Localization Microscopy for Studying Small Extracellular Vesicles

Ghanam

Chetty

Zhu

et al. 2023

Small

View full text Add to dashboard Cite

show abstract

“…The lysosomal lumen is strictly separated from the cytoplasm and other organelles to prevent hydrolytic enzymes and sequestered intracellular debris from escaping the lysosome. Lysosomal proteins are heavily glycosylated with N-and O-linked glycans (Tokhtaeva et al, 2017) and are protected from degradation by proteases (Fukuda, 1991;Reggiori et al, 2021).…”

Section: The Structure Function and Regulation Of Lysosomes In The Heartmentioning

confidence: 99%

“…Lysosomes are rarely seen 26042865 (Sesso et al, 2012) Mouse (C57BLKS/J), leptin receptor deficient (db/db), sex unknown Cardiac lysosomal protease (Cathepsin D) activity is decreased 6327362 (Skoza et al, 1980) Mouse (C57BL/6), STZ + HFD-induced, male LAMP2 expression is decreased in the diabetic heart 31564413 (Reggiori et al, 2021) Mouse (C57BLKS/J), leptin receptor deficient (db/db), sex unknown Cathepsin D expression is upregulated in the diabetic heart 31862139 (Packer, 2020) Mouse (C57BL/6), HFD-induced, male Cathepsin K knockout mitigates HFD-induced cardiac hypertrophy and dysfunction 23069627 (Tan and Finkel, 2022) Mouse (C57/BL6J), High fat and high sucrose-induced obesity, male Cathepsin B activity and LAMP2 expression are decreased, and TFEB inhibition is increased 27620487 (Sacco et al, 2003) Abbreviations: STZ, streptozotocin; HFD, high-fat diet.…”

Section: Modelmentioning

confidence: 99%

Lysosomal dysfunction in diabetic cardiomyopathy

Kobayashi

Hahn²,

Silverstein³

et al. 2023

Front. Aging

View full text Add to dashboard Cite

Diabetes is a major risk factor for a variety of cardiovascular complications, while diabetic cardiomyopathy, a disease specific to the myocardium independent of vascular lesions, is an important causative factor for increased risk of heart failure and mortality in diabetic populations. Lysosomes have long been recognized as intracellular trash bags and recycling facilities. However, recent studies have revealed that lysosomes are sophisticated signaling hubs that play remarkably diverse roles in adapting cell metabolism to an ever-changing environment. Despite advances in our understanding of the physiological roles of lysosomes, the events leading to lysosomal dysfunction and how they relate to the overall pathophysiology of the diabetic heart remain unclear and are under intense investigation. In this review, we summarize recent advances regarding lysosomal injury and its roles in diabetic cardiomyopathy.

show abstract

“…The O -GlcNAylation of several transcription factors, such as PGC1α, FoxO3, NF-κB and CREB, also indirectly participates in transcriptional regulation of metabolism [ 159 , 160 , 161 ]. Although only briefly shown in Figure 4 , it is worth noting that almost all enzymes in the TCA cycle are also modified by O -GlcNAcylation, such as AH, IDH, KGD, SL, SDH, MDH and the several subunits of respiratory chain complexes [ 162 , 163 ]. CS and FH may be potentially O -GlcNAcylatied, but there is still a lack of supporting evidence [ 152 ].…”

Section: Dynamic O -Glcnacylation Cycle and Hexosa...mentioning

confidence: 99%

O-GlcNAcylation: The Underestimated Emerging Regulators of Skeletal Muscle Physiology

Liu

Fan

et al. 2022

Cells

View full text Add to dashboard Cite

O-GlcNAcylation is a highly dynamic, reversible and atypical glycosylation that regulates the activity, biological function, stability, sublocation and interaction of target proteins. O-GlcNAcylation receives and coordinates different signal inputs as an intracellular integrator similar to the nutrient sensor and stress receptor, which target multiple substrates with spatio-temporal analysis specifically to maintain cellular homeostasis and normal physiological functions. Our review gives a brief description of O-GlcNAcylation and its only two processing enzymes and HBP flux, which will help to better understand its physiological characteristics of sensing nutrition and environmental cues. This nutritional and stress-sensitive properties of O-GlcNAcylation allow it to participate in the precise regulation of skeletal muscle metabolism. This review discusses the mechanism of O-GlcNAcylation to alleviate metabolic disorders and the controversy about the insulin resistance of skeletal muscle. The level of global O-GlcNAcylation is precisely controlled and maintained in the “optimal zone”, and its abnormal changes is a potential factor in the pathogenesis of cancer, neurodegeneration, diabetes and diabetic complications. Although the essential role of O-GlcNAcylation in skeletal muscle physiology has been widely studied and recognized, it still is underestimated and overlooked. This review highlights the latest progress and potential mechanisms of O-GlcNAcylation in the regulation of skeletal muscle contraction and structural properties.

show abstract

Glycans in autophagy, endocytosis and lysosomal functions

Cited by 18 publications

References 273 publications

Single Molecule Localization Microscopy for Studying Small Extracellular Vesicles

Single Molecule Localization Microscopy for Studying Small Extracellular Vesicles

Lysosomal dysfunction in diabetic cardiomyopathy

O-GlcNAcylation: The Underestimated Emerging Regulators of Skeletal Muscle Physiology

Contact Info

Product

Resources

About