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

Mauve/LYST limits fusion of lysosome-related organelles and promotes centrosomal recruitment of microtubule nucleating proteins.
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DOI:
10.1016/j.devcel.2021.02.019
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发表时间:
2021-04-05
期刊:
影响因子:
11.8
通讯作者:
Glover DM
Glover DM
中科院分区:
生物学1区
文献类型:
--
作者:
Lattao R;Rangone H;Llamazares S;Glover DM

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溶酶体相关细胞器(LROs)是携带组织特异性蛋白的内体室室,在Chediak-Higashi综合征(CHS)中由于LYST突变而增大。在这里,我们发现LYST的对应物Drosophila Mauve抑制卵黄颗粒(YGs)形成过程中与脂滴(ld)的囊泡融合事件,并对抗促进融合的Rab5。淡紫色定位于YGs和纺锤体极点,它与LDs成分和微管相关蛋白Minispindles/Ch-TOG共免疫沉淀。在紫红色来源的突变胚胎中,小针状体水平在增大的YGs处增加,在中心体周围减少。这导致中心体微管成核减少,这一缺陷可以通过显性阴性Rab5修复。总之,这揭示了内体囊泡和中心体之间意想不到的联系。这些发现证实了Mauve/LYST在调节LRO形成和中心体行为中的作用,这一作用可能解释了CHS患者免疫突触LRO增大和中心体定位缺陷的原因。Mauve调节溶酶体相关细胞器和脂滴融合Mauve调节PCM募集和中心体微管成核Mauve与Rab5、Msps和γ-微管蛋白相互作用Mauve/LYST对抗Rab5,促进囊泡融合影响PCM募集Lattao等人研究了Mauve的作用,Mauve是LYST基因的果蝇同源物,在尚不清楚的Chediak-Higashi综合征中发生突变。他们发现,Mauve/LYST调节着中心体的囊泡融合和微管成核,揭示了囊泡、中心体稳态和微管成核之间的重要联系。
Lysosome-related organelles (LROs) are endosomal compartments carrying tissue-specific proteins, which become enlarged in Chediak-Higashi syndrome (CHS) due to mutations in LYST. Here, we show that Drosophila Mauve, a counterpart of LYST, suppresses vesicle fusion events with lipid droplets (LDs) during the formation of yolk granules (YGs), the LROs of the syncytial embryo, and opposes Rab5, which promotes fusion. Mauve localizes on YGs and at spindle poles, and it co-immunoprecipitates with the LDs’ component and microtubule-associated protein Minispindles/Ch-TOG. Minispindles levels are increased at the enlarged YGs and diminished around centrosomes in mauve-derived mutant embryos. This leads to decreased microtubule nucleation from centrosomes, a defect that can be rescued by dominant-negative Rab5. Together, this reveals an unanticipated link between endosomal vesicles and centrosomes. These findings establish Mauve/LYST’s role in regulating LRO formation and centrosome behavior, a role that could account for the enlarged LROs and centrosome positioning defects at the immune synapse of CHS patients. Drosophila Mauve regulates lysosome-related organelle and lipid droplet fusion Mauve regulates PCM recruitment and microtubule nucleation from centrosomes Mauve interacts with Rab5, Msps, and γ-tubulin Mauve/LYST opposes Rab5, which promotes vesicle fusion affecting PCM recruitment Lattao et al. investigate the role of Mauve, the Drosophila homolog of the gene LYST, which is mutated in the poorly understood Chediak-Higashi syndrome. They show that Mauve/LYST regulates vesicle fusion and microtubule nucleation at centrosomes, revealing an important connection among vesicles, centrosome homeostasis, and microtubule nucleation.
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