Mauve/LYST limits fusion of lysosome-related organelles and promotes centrosomal recruitment of microtubule nucleating proteins

Lattao, Ramona; Rangone, Hélène; Llamazares, Salud; Glover, David M.

doi:10.1016/j.devcel.2021.02.019

Cited by 14 publications

(18 citation statements)

References 66 publications

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“…5a arrow), as well as the YV size heterogeneity and autofluorescence variability reported for stronger allele combinations (Fig. 5a) 23 , but no obvious association between GGs and LDs (Fig. 5b) 23 .…”

Section: Resultsmentioning

confidence: 68%

“…Mauve is a resident protein on lysosome related organelles (LROs) important for their maturation. YVs are a type of LRO and in the absence of Mauve display several phenotypes, including an association with LDs 23 . Might these YV-LD interactions affect nutrient sorting?…”

Section: Resultsmentioning

confidence: 99%

“…As strong disruption of Mauve severely impairs early embryonic development 23 , we generated mothers transheterozygous for two weak alleles, mauve Rosario and mauve 3 . These embryos displayed LDs association with YVs (Fig.…”

Section: Resultsmentioning

confidence: 99%

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Drosophila embryos spatially sort their nutrient stores to facilitate their utilization

Kilwein

Johnson

Thomalla

et al. 2022

Preprint

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Animal embryos are provisioned by their mothers with a diverse nutrient supply critical for development. In Drosophila, the three most abundant nutrients (triglycerides, proteins, and glycogen) are sequestered in distinct storage structures, lipid droplets (LDs), yolk vesicles (YVs) and glycogen granules (GGs). Using transmission electron microscopy as well as live and fixed-sample fluorescence imaging, we find that all three storage structures are dispersed throughout the egg but are then spatially allocated to distinct tissues by gastrulation: LDs largely to the peripheral epithelium, YVs and GGs to the central yolk cell. To confound the embryo’s ability to sort its nutrients, we employ mutants in Jabba and Mauve to generate LD:GG or LD:YV compound structures. In these mutants, LDs are missorted to the yolk cell and their turnover is delayed. Our observations demonstrate dramatic spatial nutrient sorting in early embryos and provide the first evidence for its functional importance.

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Section: Resultsmentioning

confidence: 68%

Section: Resultsmentioning

confidence: 99%

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Drosophila embryos spatially sort their nutrient stores to facilitate their utilization

Kilwein

Johnson

Thomalla

et al. 2022

Preprint

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“…Regarding cytotoxicity, although one study reported that the smaller size of the cortical actin mesh at the CS relative to the enlarged LGs prevented degranulation in CHS1/LYST -deficient NK cells ( 93 ), important roles of CHS1/LYST in LG polarization to the CS have also been suggested ( 91 ). In addition, Mauve, the Drosophila homolog of CHS1/LYST, not only regulates vesicle fusion of yolk granules (the secretory lysosomes of the Drosophila embryo) but was also found to regulate microtubule nucleation from the microtubule organizing center (MTOC) ( 94 ). Therefore, future studies are required to better elucidate the molecular details by which CHS1/LYST regulates the lysosomal fusion/fission process and the impact on cytotoxic activity.…”

Section: Biogenesis Of Lytic Granulesmentioning

confidence: 99%

Locked and Loaded: Mechanisms Regulating Natural Killer Cell Lytic Granule Biogenesis and Release

2022

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NK cell-mediated cytotoxicity is a critical element of our immune system required for protection from microbial infections and cancer. NK cells bind to and eliminate infected or cancerous cells via direct secretion of cytotoxic molecules toward the bound target cells. In this review, we summarize the current understanding of the molecular regulations of NK cell cytotoxicity, focusing on lytic granule development and degranulation processes. NK cells synthesize apoptosis-inducing proteins and package them into specialized organelles known as lytic granules (LGs). Upon activation of NK cells, LGs converge with the microtubule organizing center through dynein-dependent movement along microtubules, ultimately polarizing to the cytotoxic synapse where they subsequently fuse with the NK plasma membrane. From LGs biogenesis to degranulation, NK cells utilize several strategies to protect themselves from their own cytotoxic molecules. Additionally, molecular pathways that enable NK cells to perform serial killing are beginning to be elucidated. These advances in the understanding of the molecular pathways behind NK cell cytotoxicity will be important to not only improve current NK cell-based anti-cancer therapies but also to support the discovery of additional therapeutic opportunities.

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“…Additional theories of nucleating MTs at the cortex were recently proposed in the context of lipid droplets (LD) and yolk granules (YG) and the possibility that LD-associated proteins can exert control on MT nucleation from centrosomes [ 24 ]. One of these proteins associated with YGs was shown to be Mauve/LYST.…”

Section: Introductionmentioning

confidence: 99%

Modulating the bicoid gradient in space and time

2021

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Background The formation of the Bicoid (Bcd) gradient in the early Drosophila is one of the most fascinating observations in biology and serves as a paradigm for gradient formation, yet its mechanism is still not fully understood. Two distinct models were proposed in the past, the SDD and the ARTS model. Results We define novel cis- and trans-acting factors that are indispensable for gradient formation. The first one is the poly A tail length of the bcd mRNA where we demonstrate that it changes not only in time, but also in space. We show that posterior bcd mRNAs possess a longer poly tail than anterior ones and this elongation is likely mediated by wispy (wisp), a poly A polymerase. Consequently, modulating the activity of Wisp results in changes of the Bcd gradient, in controlling downstream targets such as the gap and pair-rule genes, and also in influencing the cuticular pattern. Attempts to modulate the Bcd gradient by subjecting the egg to an extra nuclear cycle, i.e. a 15th nuclear cycle by means of the maternal haploid (mh) mutation showed no effect, neither on the appearance of the gradient nor on the control of downstream target. This suggests that the segmental anlagen are determined during the first 14 nuclear cycles. Finally, we identify the Cyclin B (CycB) gene as a trans-acting factor that modulates the movement of Bcd such that Bcd movement is allowed to move through the interior of the egg. Conclusions Our analysis demonstrates that Bcd gradient formation is far more complex than previously thought requiring a revision of the models of how the gradient is formed.

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Mauve/LYST limits fusion of lysosome-related organelles and promotes centrosomal recruitment of microtubule nucleating proteins

Cited by 14 publications

References 66 publications

Drosophila embryos spatially sort their nutrient stores to facilitate their utilization

Drosophila embryos spatially sort their nutrient stores to facilitate their utilization

Locked and Loaded: Mechanisms Regulating Natural Killer Cell Lytic Granule Biogenesis and Release

Modulating the bicoid gradient in space and time

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