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半血细胞诱导的半乳糖凝集素在树突修剪过程中介导磷脂酰丝氨酸和 N-糖基化 Drpr/CED-1 受体。

Galectins induced from hemocytes bridge phosphatidylserine and N-glycosylated Drpr/CED-1 receptor during dendrite pruning.

机构信息

Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan.

Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan.

出版信息

Nat Commun. 2024 Aug 27;15(1):7402. doi: 10.1038/s41467-024-51581-6.

DOI:10.1038/s41467-024-51581-6
PMID:39191750
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11349873/
Abstract

During neuronal pruning, phagocytes engulf shed cellular debris to avoid inflammation and maintain tissue homeostasis. How phagocytic receptors recognize degenerating neurites had been unclear. Here, we identify two glucosyltransferases Alg8 and Alg10 of the N-glycosylation pathway required for dendrite fragmentation and clearance through genetic screen. The scavenger receptor Draper (Drpr) is N-glycosylated with complex- or hybrid-type N-glycans that interact specifically with galectins. We also identify the galectins Crouching tiger (Ctg) and Hidden dragon (Hdg) that interact with N-glycosylated Drpr and function in dendrite pruning via the Drpr pathway. Ctg and Hdg are required in hemocytes for expression and function, and are induced during dendrite injury to localize to injured dendrites through specific interaction with exposed phosphatidylserine (PS) on the surface membrane of injured dendrites. Thus, the galectins Ctg and Hdg bridge the interaction between PS and N-glycosylated Drpr, leading to the activation of phagocytosis.

摘要

在神经元修剪过程中，吞噬细胞吞噬脱落的细胞碎片，以避免炎症并维持组织内稳态。吞噬受体如何识别退化的神经突一直不清楚。在这里，我们通过遗传筛选鉴定出 N 糖基化途径中的两种葡糖基转移酶 Alg8 和 Alg10，它们是树突片段化和清除所必需的。吞噬受体 Draper（Drpr）与特定地与半乳糖凝集素相互作用的复合或混合型 N-聚糖糖基化。我们还鉴定了与 N-糖基化的 Drpr 相互作用并通过 Drpr 途径在树突修剪中发挥作用的半乳糖凝集素 Crouching tiger（Ctg）和 Hidden dragon（Hdg）。Ctg 和 Hdg 在血细胞中表达和功能所需，并在树突损伤期间被诱导，通过与损伤树突表面膜上暴露的磷脂酰丝氨酸（PS）的特异性相互作用定位于损伤的树突。因此，半乳糖凝集素 Ctg 和 Hdg 桥接 PS 和 N-糖基化的 Drpr 之间的相互作用，导致吞噬作用的激活。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be26/11349873/9a68e49c8b44/41467_2024_51581_Fig10_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be26/11349873/f1a11a36d000/41467_2024_51581_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be26/11349873/6ecf7b85b227/41467_2024_51581_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be26/11349873/ab731aa3cc70/41467_2024_51581_Fig6_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be26/11349873/be580233d0d1/41467_2024_51581_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be26/11349873/851465989d31/41467_2024_51581_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be26/11349873/9a68e49c8b44/41467_2024_51581_Fig10_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be26/11349873/c847f8a18f3d/41467_2024_51581_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be26/11349873/15a68feae422/41467_2024_51581_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be26/11349873/8ee6883cb9c3/41467_2024_51581_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be26/11349873/f1a11a36d000/41467_2024_51581_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be26/11349873/6ecf7b85b227/41467_2024_51581_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be26/11349873/ab731aa3cc70/41467_2024_51581_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be26/11349873/f132439ef6c3/41467_2024_51581_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be26/11349873/be580233d0d1/41467_2024_51581_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be26/11349873/851465989d31/41467_2024_51581_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be26/11349873/9a68e49c8b44/41467_2024_51581_Fig10_HTML.jpg

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