한빛사논문
- 조회541
Hyun Gwan Park1,4*, Yeongjin David Kim1,4*, Eunsang Cho1,4*, Ting-Yi Lu2, Chi-Kuang Yao2, Jihye Lee3, and Seungbok Lee1,4
1Department of Brain and Cognitive Sciences, Seoul National University, Seoul, Korea; 2Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan; 3Department of Oral Pathology, School of Dentistry, Pusan National University, Yangsan, Korea; 4Department of Cell and Developmental Biology and Dental Research Institute, Seoul National University, Seoul, Korea.
*H.G. Park, Y.D. Kim, and E. Cho contributed equally to this paper.
Correspondence to Seungbok Lee
Abstract
Modulation of presynaptic actin dynamics is fundamental to synaptic growth and functional plasticity; yet the underlying molecular and cellular mechanisms remain largely unknown. At Drosophila NMJs, the presynaptic Rac1-SCAR pathway mediates BMP-induced receptor macropinocytosis to inhibit BMP growth signaling. Here, we show that the Rho-type GEF Vav acts upstream of Rac1 to inhibit synaptic growth through macropinocytosis. We also present evidence that Vav-Rac1-SCAR signaling has additional roles in tetanus-induced synaptic plasticity. Presynaptic inactivation of Vav signaling pathway components, but not regulators of macropinocytosis, impairs post-tetanic potentiation (PTP) and enhances synaptic depression depending on external Ca2+ concentration. Interfering with the Vav-Rac1-SCAR pathway also impairs mobilization of reserve pool (RP) vesicles required for tetanus-induced synaptic plasticity. Finally, treatment with an F-actin–stabilizing drug completely restores RP mobilization and plasticity defects in Vav mutants. We propose that actin-regulatory Vav-Rac1-SCAR signaling independently regulates structural and functional presynaptic plasticity by driving macropinocytosis and RP mobilization, respectively.
논문정보
- Research article
- 2022년 08월 (BRIC 등록일 2022-09-05)
- 국내(교신)+국외 연구진
- 의약학 > 분자세포의학
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