Colón-Cruz Luis, Rodriguez-Morales Roberto, Santana-Cruz Alexis, Cantres-Velez Juan, Torrado-Tapias Aranza, Lin Sheng-Jia, Yudowski Guillermo, Kensler Robert, Marie Bruno, Burgess Shawn M, Renaud Olivier, Varshney Gaurav K, Behra Martine
Department of Anatomy and Neurobiology, School of Medicine, University of Puerto Rico, San Juan, Puerto Rico.
Genes & Human Disease Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, United States.
Front Mol Neurosci. 2021 Apr 20;14:624265. doi: 10.3389/fnmol.2021.624265. eCollection 2021.
The role of the cannabinoid receptor 2 (CNR2) is still poorly described in sensory epithelia. We found strong expression in hair cells (HCs) of the inner ear and the lateral line (LL), a superficial sensory structure in fish. Next, we demonstrated that sensory synapses in HCs were severely perturbed in larvae lacking cnr2. Appearance and distribution of presynaptic ribbons and calcium channels (Ca1.3) were profoundly altered in mutant animals. Clustering of membrane-associated guanylate kinase (MAGUK) in post-synaptic densities (PSDs) was also heavily affected, suggesting a role for cnr2 for maintaining the sensory synapse. Furthermore, vesicular trafficking in HCs was strongly perturbed suggesting a retrograde action of the endocannabinoid system (ECs) via cnr2 that was modulating HC mechanotransduction. We found similar perturbations in retinal ribbon synapses. Finally, we showed that larval swimming behaviors after sound and light stimulations were significantly different in mutant animals. Thus, we propose that cnr2 is critical for the processing of sensory information in the developing larva.
大麻素受体2（CNR2）在内耳和侧线（鱼类的一种浅表感觉结构）的毛细胞（HC）中的作用仍鲜为人知。我们发现它在内耳和侧线的毛细胞中有强烈表达。接下来，我们证明，在缺乏cnr2的幼虫中，毛细胞中的感觉突触受到严重干扰。在突变动物中，突触前带状物和钙通道（Ca1.3）的外观和分布发生了深刻变化。膜相关鸟苷酸激酶（MAGUK）在突触后致密物（PSD）中的聚集也受到严重影响，这表明cnr2在维持感觉突触方面发挥作用。此外，毛细胞中的囊泡运输受到强烈干扰，这表明内源性大麻素系统（ECs）通过cnr2发挥逆行作用，调节毛细胞的机械转导。我们在视网膜带状突触中也发现了类似的干扰。最后，我们表明，在声音和光刺激后，突变动物的幼虫游泳行为有显著差异。因此，我们认为cnr2对发育中的幼虫的感觉信息处理至关重要。
