Cerebellar ataxia disease-associated Snx14 promotes lipid droplet growth at ER-droplet contacts
Cerebellar ataxia disease-associated Snx14 promotes lipid droplet growth at ER-droplet contacts
复制标题
DOI：
10.1083/jcb.201808133
复制
发表时间：
2019-04-01
影响因子：
7.8
通讯作者：
Henne, W. Mike
中科院分区：
文献类型：
--
作者：
Datta, Sanchari;Liu, Yang;Henne, W. Mike
脂滴（LD）是细胞用来维持体内平衡的营养库。初生液滴在内质网（ER）上形成，并在外源性脂肪酸（FA）流入后生长。LD的萌芽需要广泛的ER-LD串扰，但如何调节仍然知之甚少。在这里，我们表明，排序连接蛋白Snx 14，ER居民蛋白与小脑共济失调SCAR 20，定位于ER-LD接触后FA治疗，在那里它促进LD成熟。使用基于邻近的APEX技术和拓扑解剖，我们发现Snx 14在ER-LD接触处特异性地积累，独立于Seipin，在那里它保持ER锚定并在反式中结合LD。SNX 14（KO）细胞表现出扰动的LD形态，而Snx 14过表达促进LD生物发生并延长ER-LD接触。多时间点成像显示，Snx 14被募集到含有脂肪酰辅酶A连接酶ACSL 3的ER微结构域，其中新生LD出芽。我们建议，Snx 14是一种新的标记ER-LD接触和调节FA刺激的LD生长。
Lipid droplets (LDs) are nutrient reservoirs used by cells to maintain homeostasis. Nascent droplets form on the endoplasmic reticulum (ER) and grow following an influx of exogenous fatty acids (FAs). The budding of LDs requires extensive ER-LD crosstalk, but how this is regulated remains poorly understood. Here, we show that sorting nexin protein Snx14, an ER-resident protein associated with the cerebellar ataxia SCAR20, localizes to ER-LD contacts following FA treatment, where it promotes LD maturation. Using proximity-based APEX technology and topological dissection, we show that Snx14 accumulates specifically at ER-LD contacts independently of Seipin, where it remains ER-anchored and binds LDs in trans. SNX14(KO) cells exhibit perturbed LD morphology, whereas Snx14 overexpression promotes LD biogenesis and extends ER-LD contacts. Multi-time point imaging reveals that Snx14 is recruited to ER microdomains containing the fatty acyl-CoA ligase ACSL3, where nascent LDs bud. We propose that Snx14 is a novel marker for ER-LD contacts and regulates FA-stimulated LD growth.