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Current Biology:标定胞外囊泡相关基因

来源:生物谷 2015-12-16 16:39

 

图片来自:jonlieffmd.com

2015年12月13日/生物谷BIOON/--几十年来,科学家们一直认为,人体细胞释放的非常微小的囊泡往往并非很重要的东西,可能仅是一些生物碎屑或者无法消化的成分。但一项发表在《Current Biology》上的研究指出,在线虫中这些囊泡有着重要作用。

囊泡,又被称为胞外囊泡(EVS),对生物可以产生有益的作用,如可以促进组织修复,或促进免疫系统功能,并可以携带疾病的信号(如癌症或神经退行性疾病)。研究人员在秀丽隐杆线虫中分离出了可以释放囊泡的细胞,并确定了335个基因与囊泡释放非常相关。这些基因提供有关囊泡的生物学功能的信息,并可以人类的一些疾病建立关联。他们发现,这335个基因中的10%参与调节囊泡的形成、释放和可能的功能。了解细胞的外排囊泡是如何释放并与其他细胞沟通的,可能揭示囊泡携带的健康信息在不同疾病人群中的差异性。

科学家仍不能确定囊泡是如何形成的,也不知道为什么囊泡中包裹的分子不同会导致不同的结果。但是,研究人员指出,使用线虫模型可能帮助解决这些问题,因为线虫中有许多基因与人类相似。本文作者之一、美国罗格斯大学Maureen Barr教授和她的同事,已经找到了囊泡携带不同分子的一个控制途径。在外排囊泡中携带的蛋白质有多种,其中有一种与人类的一种遗传学疾病多囊肾相关。多囊肾病基因产物的分泌蛋白即出现在人类细胞中,还出现在线虫细胞中,但是没人知道为什么这种蛋白会出现在外排的囊泡中。

从线虫模型开始外排囊泡的研究是个不错的开始,可以帮助我们了解囊泡的一系列问题,这些问题对于深入理解人类疾病(如多囊肾疾病)都很重要,对未来利用囊泡也有重要作用。因为囊泡被发现在各种类型的体液中,如尿液、血液和脑脊髓液,确定这些囊泡的细胞来源几乎不可能。这是为什么我们对囊泡知之甚少的原因。通过了解一个细胞将蛋白质、脂质和核酸装入囊泡并排出体外,这对于我们未来进行对癌细胞等的干预成为可能,并可以模拟细胞的囊泡外排来携带一些药物分子,这或许也是未来药物研究的方向之一。(生物谷Bioon.com)

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DOI: http://dx.doi.org/10.1016/j.cub.2015.10.057

PMC:

PMID:

Cell-Specific Transcriptional Profiling of Ciliated Sensory Neurons Reveals Regulators of Behavior and Extracellular Vesicle Biogenesis

Highlights

•Extracellular vesicle (EV)-releasing neuron (EVN) genes act in sensory signaling

•This is the first cell-specific profile of EVNs isolated from adult C. elegans

•TRAF homologs are required for polycystin-mediated male mating behaviors

•p38 MAPK PMK-1 regulates EV biogenesis independent of its canonical kinase cascade

Summary

Cilia and extracellular vesicles (EVs) are signaling organelles [ 1 ]. Cilia act as cellular sensory antennae, with defects resulting in human ciliopathies. Cilia both release and bind to EVs [ 1 ]. EVs are sub-micron-sized particles released by cells and function in both short- and long-range intercellular communication. InC. elegans and mammals, the autosomal dominant polycystic kidney disease (ADPKD) gene products polycystin-1 and polycystin-2 localize to both cilia and EVs, act in the same genetic pathway, and function in a sensory capacity, suggesting ancient conservation [ 2 ]. A fundamental understanding of EV biology and the relationship between the polycystins, cilia, and EVs is lacking. To define properties of a ciliated EV-releasing cell, we performed RNA-seq on 27 GFP-labeled EV-releasing neurons (EVNs) isolated from adult C. elegans. We identified 335 significantly overrepresented genes, of which 61 were validated by GFP reporters. The EVN transcriptional profile uncovered new pathways controlling EV biogenesis and polycystin signaling and also identified EV cargo, which included an antimicrobial peptide and ASIC channel. Tumor-necrosis-associated factor (TRAF) homologs trf-1 and trf-2 and the p38 mitogen-activated protein kinase (MAPK)pmk-1 acted in polycystin-signaling pathways controlling male mating behaviors. pmk-1 was also required for EV biogenesis, independent of the innate immunity MAPK signaling cascade. This first high-resolution transcriptome profile of a subtype of ciliated sensory neurons isolated from adult animals reveals the functional components of an EVN.

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