김동규 (서울대학교, 현 UCSF)

한빛사논문

조회363

김동규Dong Kyu Kim

서울대학교, 현 UCSF

CV File 163 kb

Exp. Mol. Med., Jul 01 2024, | https://doi.org/10.1038/s12276-024-01274-3 FGFR3 drives Aβ-induced tau uptake

Dong Kyu Kim^1,2,6, Kyujin Suh^1,2,6, Junho Park^3,4, Sang-Eun Lee^1,5, Jihui Han^1,2, Sunghoe Chang^1,5, Youngsoo Kim^3,4and Inhee Mook-Jung^1,2

¹Department of Biomedical Science, College of Medicine, Seoul National University, Seoul, Korea.

²Convergence Research Center for Dementia, Medical Research Center, Seoul National University, Seoul, Korea.

³Department of Medical Science, CHA University School of Medicine, Seongnam, Republic of Korea.

⁴Advanced Omics Center, Future Medicine Research Institute, CHA Bundang Medical Center, Seongnam, Republic of Korea.

⁵Neuroscience Research Institute, Seoul National University College of Medicine, Seoul, South Korea.

⁶These authors contributed equally: Dong Kyu Kim, Kyujin Suh.

Correspondence to Inhee Mook-Jung.

Abstract

The amyloid cascade hypothesis suggests that amyloid beta (Aβ) contributes to initiating subsequent tau pathology in Alzheimer's disease (AD). However, the underlying mechanisms through which Aβ contributes to tau uptake and propagation remain poorly understood. Here, we show that preexisting amyloid pathology accelerates the uptake of extracellular tau into neurons. Using quantitative proteomic analysis of endocytic vesicles, we reveal that Aβ induces the internalization of fibroblast growth factor receptor 3 (FGFR3). Extracellular tau binds to the extracellular domain of FGFR3 and is internalized by the FGFR3 ligand, fibroblast growth factor 2 (FGF2). Aβ accelerates FGF2 secretion from neurons, thereby inducing the internalization of tau-attached FGFR3. Knockdown of FGFR3 in the hippocampus reduces tau aggregation by decreasing tau uptake and improving memory function in AD model mice. These data suggest FGFR3 in neurons as a novel tau receptor and a key mediator of Aβ-induced tau uptake in AD.

논문정보

형식Research article
게재일2024년 07월 (BRIC 등록일 2024-07-03)
연구진국내 연구진
분야 의약학 > 신경의학

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