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LYVAC/PDZD8是一种溶酶体空泡剂
作者:小柯机器人 发布时间:2025/8/22 14:40:57


美国匹兹堡大学谭小军团队的一项最新研究探明了LYVAC/PDZD8是一种溶酶体空泡剂。2025年8月21日出版的《科学》杂志发表了这项成果。

该研究组发现,内质网(ER)锚定的含PDZ结构域的脂质转移蛋白8 (PDZD8),该研究组建议将其更名为溶酶体液泡化因子(LYVAC),是溶酶体液泡化的一般介质。利用人类细胞系,该团队发现多种溶酶体液泡化诱导剂在溶酶体渗透胁迫下聚合,通过多价相互作用触发LYVAC募集。应激诱导的溶酶体脂质信号传导有助于LYVAC的募集和激活。通过直接感知溶酶体磷脂酰丝氨酸和胆固醇,LYVAC的脂质转移域介导ER向溶酶体的定向脂质运动,导致溶酶体渗透膜扩张。这些发现揭示了溶酶体空泡化的基本机制,在病理生理学上具有广泛的意义。

据介绍,溶酶体空泡化常见于许多病理生理条件下,但其分子机制和功能在很大程度上仍然未知。

附:英文原文

Title: LYVAC/PDZD8 is a lysosomal vacuolator

Author: Haoxiang Yang, Jinrui Xun, Yajuan Li, Awishi Mondal, Bo Lv, Simon C. Watkins, Lingyan Shi, Jay Xiaojun Tan

Issue&Volume: 2025-08-21

Abstract: Lysosomal vacuolation is commonly found in many pathophysiological conditions, but its molecular mechanisms and functions remain largely unknown. Here, we show that the endoplasmic reticulum (ER)–anchored lipid transfer protein PDZ domain–containing 8 (PDZD8), which we propose to be renamed as lysosomal vacuolator (LYVAC), is a general mediator of lysosomal vacuolation. Using human cell lines, we found that diverse lysosomal vacuolation inducers converged on lysosomal osmotic stress, triggering LYVAC recruitment through multivalent interactions. Stress-induced lysosomal lipid signaling contributed to both the recruitment and activation of LYVAC. By directly sensing lysosomal phosphatidylserine and cholesterol, the lipid transfer domain of LYVAC mediated directional ER-to-lysosome lipid movement, leading to osmotic membrane expansion of lysosomes. These findings uncover an essential mechanism for lysosomal vacuolation with broad implications in pathophysiology.

DOI: adz0972

Source: https://www.science.org/doi/10.1126/science.adz0972

期刊信息
Science:《科学》,创刊于1880年。隶属于美国科学促进会,最新IF:63.714