Reciprocal control of excitatory synapse numbers by Wnt and Wnt inhibitor PRR7 secreted on exosomes
- 주제(기타) Multidisciplinary Sciences
- 설명문(일반) [Lee, Sang H.; Shin, Seung Min; Zhong, Peng; Kim, Dong-Il; Liu, Qing-Song] Med Coll Wisconsin, Dept Pharmacol & Toxicol, 8701 Watertown Plank Rd, Milwaukee, WI 53226 USA; [Lee, Sang H.; Liu, Qing-Song] Med Coll Wisconsin, Neurosci Res Ctr, 8701 Watertown Plank Rd, Milwaukee, WI 53226 USA; [Kim, Hyun-Taek; Kim, Cheol-Hee] Chungnam Natl Univ, Dept Biol, Daejeon 34134, South Korea; [Kim, June Myoung; Kim, Dae-Won] Yonsei Univ, Dept Biochem, Seoul 03722, South Korea; [Heo, Won Do] Korea Adv Inst Sci & Technol, Dept Biol Sci, Daejeon 34141, South Korea; [Yeo, Chang-Yeol] Ewha Womans Univ, Dept Life Sci, Seoul 03760, South Korea; [Yeo, Chang-Yeol] Ewha Womans Univ, Res Ctr Cellular Homeostasis, Seoul 03760, South Korea
- 등재 SCIE, SCOPUS
- 발행기관 NATURE PUBLISHING GROUP
- 발행년도 2018
- URI http://www.dcollection.net/handler/ewha/000000155997
- 본문언어 영어
- Published As http://dx.doi.org/10.1038/s41467-018-05858-2
초록/요약
Secreted Wnts play crucial roles in synaptogenesis and synapse maintenance, but endogenous factors promoting synapse elimination in central neurons remain unknown. Here we show that proline-rich 7 (PRR7) induces specific removal of excitatory synapses and acts as a Wnt inhibitor. Remarkably, transmembrane protein PRR7 is activity-dependently released by neurons via exosomes. Exosomal PRR7 is uptaken by neurons through membrane fusion and eliminates excitatory synapses in neighboring neurons. Conversely, PRR7 knockdown in sparse neurons greatly increases excitatory synapse numbers in all surrounding neurons. These non-cell autonomous effects of PRR7 are effectively negated by augmentation or blockade of Wnt signaling. PRR7 exerts its effect by blocking the exosomal secretion of Wnts, activation of GSK3 beta, and promoting proteasomal degradation of PSD proteins. These data uncover a proximity-dependent, reciprocal mechanism for the regulation of excitatory synapse numbers in local neurons and demonstrate the significance of exosomes in interneuronal signaling in the vertebrate brain.
more