장성호 교수
Sunghoe Chang
서울대학교 생리학과 · 생화학·유전·분자생물학
연구실 소개
장성호 교수의 연구실은 신경전달물질 방출의 분자 기반을 규명하는 데 초점을 맞추고 있으며, 특히 시냅스 소포의 형성, 운반, 재활용 및 활성부위 정리 과정에서 핵심적인 역할을 하는 단백질들(예: Synapsin, SNX9, SCAMP5, ARF6 등)의 기능과 상호작용 메커니즘을 생물물리학적·세포생물학적 접근을 통해 연구하고 있습니다. 특히 시냅스 소포 집합체의 상전이적 특성, 시냅스 소포 재활용 과정에서의 조절 메커니즘, 그리고 시냅스 구조와 기능의 동적 조절을 중심으로 신경계의 기초 생리학적 메커니즘을 밝히는 데 기여하고 있습니다.
연구 현황
연구 성과 추이
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주요 논문
15Clusters of tightly packed synaptic vesicles (SVs) are a defining feature of nerve terminals. While SVs are mobile within the clusters, the clusters have no boundaries consistent with a liquid phase. We previously found that purified synapsin, a peripheral SV protein, can assemble into liquid condensates and trap liposomes into them. How this finding relates to the physiological formation of SV clusters in living cells remains unclear. Here, we report that synapsin alone, when expressed in fibro
Sorting nexin 9 (SNX9) is a member of the sorting nexin family of proteins, each of which contains a characteristic Phox homology domain. SNX9 is widely expressed and plays a role in clathrin-mediated endocytosis, but it is not known if it is present in neuronal cells. We report that SNX9 is expressed in the presynaptic compartment of cultured hippocampal neurons, where it binds to dynamin-1 and N-WASP. Overexpression of full-length SNX9 or a C-terminal truncated version caused severe defects in
The transport of axonal microtubules in growing neurites has been a controversial issue because of clear but conflicting results obtained with fluorescence-marking techniques. We have attempted to resolve the discordance via analysis of the relationship between apparent microtubule translocation and cell adhesion. Neuronal cultures were prepared from Xenopus embryos 1 d after injection of Cy3-conjugated tubulin into one of the blastomeres of two-cell-stage embryos. Anterograde translocation of a
Recent studies have reported conflicting results regarding the role of ARF6 in dendritic spine development, but no clear answer for the controversy has been suggested. We found that ADP-ribosylation factor 6 (ARF6) either positively or negatively regulates dendritic spine formation depending on neuronal maturation and activity. ARF6 activation increased the spine formation in developing neurons, whereas it decreased spine density in mature neurons. Genome-wide microarray analysis revealed that A
Calcyon, once known for interacting directly with the dopamine D1 receptor (D1DR), is implicated in various neuropsychiatric disorders including schizophrenia, bipolar disorder, and attention deficit hyperactivity disorder. Although its direct interaction with D1DR has been shown to be misinterpreted, it still plays important roles in D1DR signaling. Here, we found that calcyon interacts with the PSD-95 and subsequently forms a ternary complex with D1DR through PSD-95. Calcyon is phosphorylated
Despite being a highly enriched synaptic vesicle (SV) protein and a candidate gene for autism, the physiological function of SCAMP5 remains mostly enigmatic. Here, using optical imaging and electrophysiological experiments, we demonstrate that SCAMP5 plays a critical role in release site clearance at the active zone. Truncation analysis revealed that the 2/3 loop domain of SCAMP5 directly interacts with adaptor protein 2, and this interaction is critical for its role in release site clearance. K
Although quantum dots (QDs) have provided invaluable information regarding the diffusive behaviors of postsynaptic receptors, their application in presynaptic terminals has been rather limited. In addition, the diffraction-limited nature of the presynaptic bouton has hampered detailed analyses of the behaviors of synaptic vesicles (SVs) at synapses. Here, we created a quantum-dot based presynaptic probe and characterized the dynamic behaviors of individual SVs. As previously reported, the SVs ex
Various optical clearing approaches have been introduced to meet the growing demand for 3D volume imaging of biological structures. Each has its own strengths but still suffers from low transparency, long incubation time, processing complexity, tissue deformation, or fluorescence quenching, and a single solution that best satisfies all aspects has yet been developed. Here, we develop OptiMuS, an optimized single-step solution that overcomes the shortcomings of the existing aqueous-based clearing
α-Synuclein (α-syn) can be secreted from neurons into the extracellular space, affecting the homeostasis of neighboring cells, but the pathophysiology of secreted α-syn remains largely unknown. We found that when exogenously applied to COS-7 cells, α-syn secreted from differentiated SH-SY5Y cells was taken up by dynamin-dependent endocytosis. Upon internalization, α-syn significantly increased the rate of transferrin receptor (TfR) internalization and recycling, and subsequently the surface leve
SNX26, a brain-enriched RhoGAP, plays a key role in dendritic arborization during early neuronal development in the neocortex. In mature neurons, it is localized to dendritic spines, but little is known about its role in later stages of development. Our results show that SNX26 interacts with PSD-95 in dendritic spines of cultured hippocampal neurons, and as a GTPase-activating protein for Cdc42, it decreased the F-actin content in COS-7 cells and in dendritic spines of neurons. Overexpression of
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