初级纤毛（以下简称纤毛）是一种类似天线的细胞器，可调节细胞内反应，包括自噬，这是一种对细胞稳态至关重要的溶酶体降解过程。纤毛功能障碍与自噬损伤和称为“纤毛病”的疾病有关。纤毛基部自噬相关蛋白的发现表明，其在协调自噬启动以响应病理生理学刺激方面具有潜在作用。其中一种蛋白质是 beclin-1 (BECN1)，它是自噬体生物发生所必需的。此外，多囊蛋白-2 (PKD2)（一种在纤毛处富集的钙通道）是诱导肾细胞和癌细胞自噬所必需的且足以诱导自噬。我们之前证明 PKD2 和 BECN1 在非纤毛细胞的内质网形成蛋白质复合物，并在那里启动自噬，但这种蛋白质复合物是否存在于纤毛中仍然未知。厌食原阿黑皮质素 (POMC) 神经元是纤毛细胞，需要自噬来维持细胞内稳态。 POMC 神经元对代谢变化敏感，调节对控制食物摄入至关重要的信号通路。接触饱和脂肪酸棕榈酸 (PA) 会减少纤毛生成并抑制这些细胞的自噬。在这里，我们证明 PKD2 和 BECN1 在 N43/5 细胞（POMC 神经元的体外模型）中形成蛋白质复合物，并且 PKD2 和 BECN1 都位于纤毛。此外，我们的数据表明，纤毛是 PKD2-BECN1 蛋白复合物形成所必需的，并且 PA 会破坏 PKD2-BECN1 复合物，抑制自噬。我们的研究结果为下丘脑神经元细胞中纤毛控制自噬的机制提供了新的见解。版权所有 © 2024。由 Elsevier B.V. 出版。

The primary cilium, hereafter cilium, is an antenna-like organelle that modulates intracellular responses, including autophagy, a lysosomal degradation process essential for cell homeostasis. Dysfunction of the cilium is associated with impairment of autophagy and diseases known as "ciliopathies". The discovery of autophagy-related proteins at the base of the cilium suggests its potential role in coordinating autophagy initiation in response to physiopathological stimuli. One of these proteins, beclin-1 (BECN1), it which is necessary for autophagosome biogenesis. Additionally, polycystin-2 (PKD2), a calcium channel enriched at the cilium, is required and sufficient to induce autophagy in renal and cancer cells. We previously demonstrated that PKD2 and BECN1 form a protein complex at the endoplasmic reticulum in non-ciliated cells, where it initiates autophagy, but whether this protein complex is present at the cilium remains unknown. Anorexigenic pro-opiomelanocortin (POMC) neurons are ciliated cells that require autophagy to maintain intracellular homeostasis. POMC neurons are sensitive to metabolic changes, modulating signaling pathways crucial for controlling food intake. Exposure to the saturated fatty acid palmitic acid (PA) reduces ciliogenesis and inhibits autophagy in these cells. Here, we show that PKD2 and BECN1 form a protein complex in N43/5 cells, an in vitro model of POMC neurons, and that both PKD2 and BECN1 locate at the cilium. In addition, our data show that the cilium is required for PKD2-BECN1 protein complex formation and that PA disrupts the PKD2-BECN1 complex, suppressing autophagy. Our findings provide new insights into the mechanisms by which the cilium controls autophagy in hypothalamic neuronal cells.Copyright © 2024. Published by Elsevier B.V.