http://chineseinput.net/에서 pinyin(병음)방식으로 중국어를 변환할 수 있습니다.
변환된 중국어를 복사하여 사용하시면 됩니다.
- 中文 을 입력하시려면 zhongwen을 입력하시고 space를누르시면됩니다.
- 北京 을 입력하시려면 beijing을 입력하시고 space를 누르시면 됩니다.
RISS 인기검색어
- 검색키워드
- 저자 : Lee Unghwi (검색결과 3 건)
- 무료
- 기관 내 무료
- 유료
-
nArgBP2 regulates excitatory synapse formation by controlling dendritic spine morphology
Lee, Sang-Eun,Kim, Yoonju,Han, Jeong-Kyu,Park, Hoyong,Lee, Unghwi,Na, Myeongsu,Jeong, Soomin,Chung, ChiHye,Cestra, Gianluca,Chang, Sunghoe National Academy of Sciences 2016 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF Vol.113 No.24
<P>Neural Abelson-related gene-binding protein 2 (nArgBP2) was originally identified as a protein that directly interacts with synapseassociated protein 90/postsynaptic density protein 95-associated protein 3 (SAPAP3), a postsynaptic scaffolding protein critical for the assembly of glutamatergic synapses. Although genetic deletion of nArgBP2 in mice leads to manic/bipolar-like behaviors resembling many aspects of symptoms in patients with bipolar disorder, the actual function of nArgBP2 at the synapse is completely unknown. Here, we found that the knockdown (KD) of nArgBP2 by specific small hairpin RNAs (shRNAs) resulted in a dramatic change in dendritic spine morphology. Reintroducing shRNA-resistant nArgBP2 reversed these defects. In particular, nArgBP2 KD impaired spinesynapse formation such that excitatory synapses terminated mostly at dendritic shafts instead of spine heads in spiny neurons, although inhibitory synapse formation was not affected. nArgBP2 KD further caused a marked increase of actin cytoskeleton dynamics in spines, which was associated with increased Wiskott-Aldrich syndrome protein-family verprolin homologous protein 1 (WAVE1)/p21-activated kinase (PAK) phosphorylation and reduced activity of cofilin. These effects of nArgBP2 KD in spines were rescued by inhibiting PAK or activating cofilin combined with sequestration of WAVE. Together, our results suggest that nArgBP2 functions to regulate spine morphogenesis and subsequent spine-synapse formation at glutamatergic synapses. They also raise the possibility that the aberrant regulation of synaptic actin filaments caused by reduced nArgBP2 expression may contribute to the manifestation of the synaptic dysfunction observed in manic/bipolar disorder.</P>
-
Cho Eunji,Lee Sang Eun,Lee Unghwi,Goh Yuna,Jeong Seonyoung,Choi Junyoung,Jeong Won-Ki,Chang Sunghoe 생화학분자생물학회 2023 Experimental and molecular medicine Vol.55 No.-
nArgBP2, a candidate gene for intellectual disability, is a postsynaptic protein critical for dendritic spine development and morphogenesis, and its knockdown (KD) in developing neurons severely impairs spine-bearing excitatory synapse formation. Surprisingly, nArgBP2 KD in mature neurons did not cause morphological defects in the existing spines at rest, raising questions of how it functions in mature neurons. We found that unlike its inaction at rest, nArgBP2 KD completely inhibited the enlargement of dendritic spines during chemically induced long-term potentiation (cLTP) in mature neurons. We further found that nArgBP2 forms condensates in dendritic spines and that these condensates are dispersed by cLTP, which spatiotemporally coincides with spine head enlargement. Condensates with CaMKII phosphorylation-deficient mutant or CaMKII inhibition are neither dispersed nor accompanied by spine enlargement during cLTP. We found that nArgBP2 condensates in spines exhibited liquid-like properties, and in heterologous and in vitro expression systems, nArgBP2 undergoes liquid-liquid phase separation via multivalent intermolecular interactions between SH3 domains and proline-rich domains. It also forms coacervates with CaMKIIα, which is rapidly dissembled by calcium/CaMKIIα-dependent phosphorylation. We further showed that the interaction between nArgBP2 and WAVE1 competes with nArgBP2 phase separation and that blocking the nArgBP2-WAVE1 interaction prevents spine enlargement during cLTP. Together, our results suggest that nArgBP2 at rest is confined to the condensates but is released by CaMKIIα-mediated phosphorylation during synaptic plasticity, which regulates its timely interaction with WAVE1 to induce spine head enlargement in mature neurons.
-
Park, Daehun,Na, Myeongsu,Kim, Jung Ah,Lee, Unghwi,Cho, Eunji,Jang, Mirye,Chang, Sunghoe AAAS 2017 Science signaling Vol.10 No.487
<P><B>Amyloid-β and intersynaptic trafficking</B></P><P>Synaptic loss and dysfunction as well as neuronal accumulation of amyloid-β (Aβ) are classic features of Alzheimer’s disease (AD). Synaptic components are transported along axons in actin- and synapsin-associated vesicles to adjust synaptic strength in response to activity and to promote the formation of new synapses. Using hippocampal neurons isolated from rats and mouse models of AD, Park <I>et al</I>. found that a soluble form of Aβ impedes Ca<SUP>2+</SUP> clearance from neurons, which led to activation of the kinase CaMKIV. CaMKIV-mediated phosphorylation of synapsin caused its dissociation from synaptic vesicles and actin, thereby impairing vesicular transport. Targeting this pathway might suppress the pathological effects of Aβ in patients with AD.</P><P>The prefibrillar form of soluble amyloid-β (sAβ<SUB>1–42</SUB>) impairs synaptic function and is associated with the early phase of Alzheimer’s disease (AD). We investigated how sAβ<SUB>1–42</SUB> led to presynaptic defects using a quantum dot–based, single particle–tracking method to monitor synaptic vesicle (SV) trafficking along axons. We found that sAβ<SUB>1–42</SUB> prevented new synapse formation induced by chemical long-term potentiation (cLTP). In cultured rat hippocampal neurons, nanomolar amounts of sAβ<SUB>1–42</SUB> impaired Ca<SUP>2+</SUP> clearance from presynaptic terminals and increased the basal Ca<SUP>2+</SUP> concentration. This caused an increase in the phosphorylation of Ca<SUP>2+</SUP>/calmodulin-dependent protein kinase IV (CaMKIV) and its substrate synapsin, which markedly inhibited SV trafficking along axons between synapses. Neurons derived from a transgenic AD mouse model had similar defects, which were prevented by an inhibitor of CaMK kinase (CaMKK; which activates CaMKIV), by antibodies against Aβ<SUB>1–42</SUB>, or by expression a phosphodeficient synapsin mutant. The CaMKK inhibitor also abolished the defects in activity-dependent synaptogenesis caused by sAβ<SUB>1–42</SUB>. Our results suggest that by disrupting SV reallocation between synapses, sAβ<SUB>1–42</SUB> prevents neurons from forming new synapses or adjusting strength and activity among neighboring synapses. Targeting this mechanism might prevent synaptic dysfunction in AD patients.</P>
연관 검색어 추천
이 검색어로 많이 본 자료
활용도 높은 자료
