Regulation of Endosomal Trafficking by Rab7 and Its Effectors in Neurons: Clues from Charcot–Marie–Tooth 2B Disease DOI Creative Commons
Ryan J. Mulligan, Bettina Winckler

Biomolecules, Год журнала: 2023, Номер 13(9), С. 1399 - 1399

Опубликована: Сен. 16, 2023

Intracellular endosomal trafficking controls the balance between protein degradation and synthesis, i.e., proteostasis, but also many of cellular signaling pathways that emanate from activated growth factor receptors after endocytosis. Endosomal trafficking, sorting, motility are coordinated by activity small GTPases, including Rab proteins, whose function as molecular switches direct at membranes through effector proteins. Rab7 is particularly important in coordination degradative functions pathway. effectors control maturation properties late lysosomal compartments, such recycling, motility, fusion with downstream compartments. The spatiotemporal regulation receptor challenging neurons because their enormous size, distinct intracellular domains unique requirements (dendrites vs. axons), long lifespans postmitotic, differentiated cells. In Charcot–Marie–Tooth 2B disease (CMT2B), familial missense mutations cause alterations GTPase cycling leading to an ulcero-mutilating peripheral neuropathy. prevailing hypothesis account for CMT2B pathologies CMT2B-associated alleles alter endocytic neurotrophin NGF its TrkA and, thereby, disrupt normal trophic nervous system, other Rab7-dependent impacted. Here, using a prototypical cargo, we review physiologic interactions neurons. Since among largest cells body, place particular emphasis on temporal spatial sorting neuronal processes. We further discuss current findings mutant models, impact or balance, how this dysregulation may confer disease.

Язык: Английский

Mitochondrial cholesterol: Metabolism and impact on redox biology and disease DOI Creative Commons
Leire Goicoechea, Laura Conde de la Rosa, Sandra Torres

и другие.

Redox Biology, Год журнала: 2023, Номер 61, С. 102643 - 102643

Опубликована: Фев. 24, 2023

Cholesterol is a crucial component of membrane bilayers by regulating their structural and functional properties. traffics to different cellular compartments including mitochondria, whose cholesterol content low compared other cell membranes. Despite the limited availability in inner mitochondrial (IMM), metabolism IMM plays important physiological roles, acting as precursor for synthesis steroid hormones neurosteroids steroidogenic tissues specific neurons, respectively, or bile acids through an alternative pathway liver. Accumulation mitochondria above levels has negative impact on function several mechanisms, limitation antioxidant defenses, such glutathione redox cycle, increased generation reactive oxygen species consequent oxidative modification cardiolipin, defective assembly respiratory supercomplexes. These adverse consequences trafficking trigger onset stress death, and, ultimately, contribute development diverse diseases, metabolic liver diseases (i.e. fatty disease cancer), well lysosomal disorders Niemann-Pick type C disease) neurodegenerative Alzheimer's disease). In this review, we summarize regulation its potential diseases.

Язык: Английский

Процитировано

79
ARMH3-mediated recruitment of PI4KB directs Golgi-to-endosome trafficking and activation of the antiviral effector STING DOI Creative Commons

Run Fang,

Qifei Jiang,

Xinying Jia

и другие.

Immunity, Год журнала: 2023, Номер 56(3), С. 500 - 515.e6

Опубликована: Март 1, 2023

Язык: Английский

Процитировано

60
ER as master regulator of membrane trafficking and organelle function DOI Creative Commons
Eva M. Wenzel, Liv Anker Elfmark, Harald Stenmark

и другие.

The Journal of Cell Biology, Год журнала: 2022, Номер 221(10)

Опубликована: Авг. 23, 2022

The endoplasmic reticulum (ER), which occupies a large portion of the cytoplasm, is cell’s main site for biosynthesis lipids and carbohydrate conjugates, it essential folding, assembly, biosynthetic transport secreted proteins integral membrane proteins. discovery abundant contact sites (MCSs) between ER other compartments has revealed that, in addition to its secretory functions, plays key roles regulation organelle dynamics functions. In this review, we will discuss how regulates endosomes, lysosomes, autophagosomes, mitochondria, peroxisomes, Golgi apparatus via MCSs. Such occurs lipid Ca2+ transfer also control trans dephosphorylation reactions motility, positioning, fusion, fission. diverse controls organelles MCSs manifest as master regulator biology.

Язык: Английский

Процитировано

70
The activation of the adaptor protein STING depends on its interactions with the phospholipid PI4P DOI Open Access
Rutger D. Luteijn, Sypke R. van Terwisga, Jill E. Ver Eecke

и другие.

Science Signaling, Год журнала: 2024, Номер 17(827)

Опубликована: Март 12, 2024

Activation of the endoplasmic reticulum (ER)-resident adaptor protein STING, a component cytosolic DNA-sensing pathway, induces transcription genes encoding type I interferons (IFNs) and other proinflammatory factors. Because STING is activated at Golgi apparatus, control localization activation important in stimulating antiviral antitumor immune responses. Through genome-wide CRISPR interference screen, we found that required Golgi-resident ACBD3, which promotes generation phosphatidylinositol 4-phosphate (PI4P) trans-Golgi network, as well PI4P-associated proteins. Appropriate apparatus ACBD3 PI4P-generating kinase PI4KB. In contrast, was enhanced when lipid-shuttling OSBP, removes PI4P from inhibited by US Food Drug Administration-approved antifungal itraconazole. The increase abundance STING-activating phospholipids network resulted increased production IFN-β cytokines THP-1 cells. Furthermore, mutant could not bind to failed traffic ER response agonist, whereas forced relocalization PI4P-enriched areas elicited absence stimulation with agonist. Thus, critical for activation, manipulating may therapeutically modulate STING-dependent

Язык: Английский

Процитировано

15
PI4P/PS countertransport by ORP10 at ER–endosome membrane contact sites regulates endosome fission DOI Creative Commons
Asami Kawasaki, A. Sakai, Hiroki Nakanishi

и другие.

The Journal of Cell Biology, Год журнала: 2021, Номер 221(1)

Опубликована: Ноя. 24, 2021

Membrane contact sites (MCSs) serve as a zone for nonvesicular lipid transport by oxysterol-binding protein (OSBP)-related proteins (ORPs). ORPs mediate countertransport, in which two distinct lipids are transported counterdirectionally. How such countertransport controls specific biological functions, however, remains elusive. We report that ORP10 at ER–endosome MCSs regulates retrograde membrane trafficking. ORP10, together with ORP9 and VAP, formed phosphatidylinositol 4-phosphate (PI4P)-dependent manner. exhibited exchange activity toward its ligands, PI4P phosphatidylserine (PS), between liposomes vitro, the ER endosomes situ. Cell analysis demonstrated supplies pool of PS from ER, PI4P, to where PS-binding EHD1 is recruited facilitate endosome fission. Our study highlights novel nonenzymatic PI4P-to-PS conversion mechanism organizes remodeling during

Язык: Английский

Процитировано

54
Regulation of cellular cholesterol distribution via non-vesicular lipid transport at ER-Golgi contact sites DOI Creative Commons
Tomoki Naito, Haoning Yang, Dylan Hong Zheng Koh

и другие.

Nature Communications, Год журнала: 2023, Номер 14(1)

Опубликована: Сен. 21, 2023

Abstract Abnormal distribution of cellular cholesterol is associated with numerous diseases, including cardiovascular and neurodegenerative diseases. Regulated transport critical for maintaining its proper in the cell, yet underlying mechanisms remain unclear. Here, we show that lipid transfer proteins, namely ORP9, OSBP, GRAMD1s/Asters (GRAMD1a/GRAMD1b/GRAMD1c), control non-vesicular at points contact between ER trans-Golgi network (TGN), thereby distribution. ORP9 localizes to TGN via interaction tandem α-helices ORP10/ORP11. extracts PI4P from prevent overaccumulation suppresses OSBP-mediated PI4P-driven Golgi. By contrast, GRAMD1s excess Golgi ER, preventing build-up. Cells lacking exhibit accumulation Golgi, which further enhanced by additional depletion major plasma membrane. This accompanied chronic activation SREBP-2 signalling pathway. Our findings reveal importance regulated ER-Golgi contacts homeostasis.

Язык: Английский

Процитировано

22
A combined lipidomic and proteomic profiling of Arabidopsis thaliana plasma membrane DOI

Delphine Bahammou,

Ghislaine Recorbet, Adiilah Mamode Cassim

и другие.

The Plant Journal, Год журнала: 2024, Номер 119(3), С. 1570 - 1595

Опубликована: Май 18, 2024

SUMMARY The plant plasma membrane (PM) plays a key role in perception of environmental signals, and set‐up adaptive responses. An exhaustive quantitative description the whole set lipids proteins constituting PM is necessary to understand how these components allow fulfill such essential physiological functions. Here we provide by state‐of‐the‐art approaches first combined reference lipidome proteome from Arabidopsis thaliana suspension cell culture. We identified quantified reproducible core 2165 proteins, which far largest available data concerning this proteome. Using same samples, lipidomic approaches, allowing identification quantification an unprecedented repertoire 414 molecular species showed that sterols, phospholipids, sphingolipids are present similar proportions PM. Within each lipid class, precise amount family relative proportion were further determined, establish complete PM, highlighting specific characteristics different lipids. Results obtained point finely tuned adjustment proteins. More than hundred related metabolism, transport, or signaling have been put perspective with they associated. This represents innovative resource guide research organization functions

Язык: Английский

Процитировано

8
Emerging functions of the mitochondria–ER–lipid droplet three‐way junction in coordinating lipid transfer, metabolism, and storage in cells DOI Creative Commons
Vera F. Monteiro-Cardoso, Francesca Giordano

FEBS Letters, Год журнала: 2024, Номер 598(10), С. 1252 - 1273

Опубликована: Май 1, 2024

Over the past two decades, we have witnessed a growing appreciation for importance of membrane contact sites (CS) in facilitating direct communication between organelles. CS are tiny regions where membranes organelles meet but do not fuse and allow transfer metabolites organelles, playing crucial roles coordination cellular metabolic activities. The significant advancements imaging techniques molecular cell biology research revealed that more complex than what originally thought, as they extremely dynamic, can remodel their shape, composition, functions accordance with environmental changes occur Here, describe how recent studies led to identification three-way mitochondria-ER-lipid droplet discuss emerging these contacts maintaining lipid storage, homeostasis, balance. We also summarize properties key protein components localized at interface, special focus on proteins. Understanding tripartite is essential unraveling complexities inter-organelle cooperation within cells.

Язык: Английский

Процитировано

7
ER-Golgi-localized proteins TMED2 and TMED10 control the formation of plasma membrane lipid nanodomains DOI Creative Commons
Muhammad Anwar, Oksana A. Sergeeva, Laurence Abrami

и другие.

Developmental Cell, Год журнала: 2022, Номер 57(19), С. 2334 - 2346.e8

Опубликована: Сен. 28, 2022

To promote infections, pathogens exploit host cell machineries such as structural elements of the plasma membrane. Studying these interactions and identifying molecular players are ideal for gaining insights into fundamental biology cell. Here, we used anthrax toxin to screen a library 1,500 regulatory, cell-surface, membrane trafficking genes their involvement in intoxication process. We found that endoplasmic reticulum (ER)-Golgi-localized proteins TMED2 TMED10 required oligomerization at human cells, an essential step dependent on localization cholesterol-rich lipid nanodomains. Biochemical, morphological, mechanistic analyses showed components supercomplex operates exchange both cholesterol ceramides ER-Golgi contact sites. Overall, this study led discovery compositional remodeling interfaces fully controls formation functional nanodomains surface.

Язык: Английский

Процитировано

27
ORP9 and ORP10 form a heterocomplex to transfer phosphatidylinositol 4-phosphate at ER-TGN contact sites DOI

Ruyue He,

Furong Liu, Hui Wang

и другие.

Cellular and Molecular Life Sciences, Год журнала: 2023, Номер 80(3)

Опубликована: Фев. 28, 2023

Язык: Английский

Процитировано

13