Extracellular vesicles (EVs) are emerging as a universal means of cell to cell communication and hold great potential in diagnostics and regenerative therapies. An urgent need in the field is a fundamental understanding of physiological mechanisms driving EV generation and function. Ciliary EVs act as signaling devices in Chlamydomonas and C. elegans. Mammalian cilia shed EVs to eliminate unwanted receptors or to retract cilia before entering the cell cycle. Here we used our established C. elegans model to study sensory evoked ciliary EV release and targeting using a fluorescently labeled EV cargo polycystin-2 (PKD-2). In C. elegans and mammals, the Autosomal Dominant Polycystic Kidney Disease (ADPKD) gene products polycystin-1 and polycystin-2 localize to cilia and EVs, act in the same genetic pathway, and function in a sensory capacity, suggesting ancient conservation. We find that males deposit PKD-2-carrying EVs onto the vulva of the hermaphrodite during mating. We also show that mechanical stimulation triggers release of PKD-2-carrying EVs from cilia. To our knowledge this is the first report of mechanoresponsive nature of the ciliary EV release and of ciliary EV directional transfer from one animal to another animal. Since the polycystins are evolutionarily conserved ciliary EV cargoes, our findings suggest that similar mechanisms for EV release and targeting may occur in other systems and biological contexts.

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Polycystin-2睫状细胞外囊泡的释放和靶向

细胞外囊泡（EVs）逐渐成为一种普遍的细胞间通讯方式，在诊断和再生疗法中具有巨大潜力。该领域的迫切需求是对驱动电动汽车产生和功能的生理机制的基本理解。睫状电动车在衣藻和秀丽隐杆线虫中充当信号装置。哺乳动物的纤毛脱落EV可以消除不需要的受体或在进入细胞周期之前收回纤毛。在这里，我们使用已建立的秀丽隐杆线虫模型，使用荧光标记的EV货物多囊藻蛋白2（PKD-2）研究感觉诱发的睫状EV释放和靶向。在秀丽隐杆线虫和哺乳动物中，常染色体显性多囊肾病（ADPKD）基因产物polycystin-1和polycystin-2定位于纤毛和EV，以相同的遗传途径起作用，并具有感觉能力，建议古代保护。我们发现，雄性在交配期间会将携带PKD-2的电动汽车沉积到雌雄同体的外阴上。我们还显示机械刺激触发从纤毛释放携带PKD-2的电动汽车。据我们所知，这是关于睫状EV释放的机械响应特性以及从一种动物到另一种动物的睫状EV定向转移的首次报道。由于多囊藻毒素是进化上保守的睫状EV货物，因此我们的发现表明，在其他系统和生物学环境中，可能存在类似的EV释放和靶向机制。据我们所知，这是关于睫状EV释放的机械响应特性以及从一种动物到另一种动物的睫状EV定向转移的首次报道。由于多囊藻毒素是进化上保守的睫状EV货物，因此我们的发现表明，在其他系统和生物学环境中，可能存在类似的EV释放和靶向机制。据我们所知，这是关于睫状EV释放的机械响应特性以及从一种动物到另一种动物的睫状EV定向转移的首次报道。由于多囊藻毒素是进化上保守的睫状EV货物，因此我们的发现表明，在其他系统和生物学环境中，可能存在类似的EV释放和靶向机制。