TY - JOUR
T1 - Caveolin-1 Promotes Early Neuronal Maturation via Caveolae-Independent Trafficking of N-Cadherin and L1
AU - Shikanai, Mima
AU - Nishimura, Yoshiaki V.
AU - Sakurai, Miwa
AU - Nabeshima, Yo ichi
AU - Yuzaki, Michisuke
AU - Kawauchi, Takeshi
N1 - Funding Information:
We thank R.L. Huganir, K. Kaibuchi, and D.L. Turner for providing the plasmids and Ruth T. Yu for proofreading the manuscript. We also thank the Core Instrumentation Facility, Keio University School of Medicine, for help with Leica SP5 confocal microscopy. This work was supported by JSPS KAKENHI Grant Numbers JP26290015 (to T.K.), JP26110718 (to T.K.), JP26115004 (to Y-i.N.), JP15H05772 (to M.Y.) and Grant-in-Aid for Scientific Research on Innovation Areas “Dynamic regulation of Brain Function by Scrap & Build System” ( JP17H05757 to T.K. and JP16H06461 to M.Y.) from The Ministry of Education, Culture, Sports, Science, and Technology of Japan (MEXT) and by grants from the JST-PRESTO (to T.K.), AMED under Grant Number JP18gm5010002 (to T.K.), and the Takeda Science Foundation (to T.K.).
Publisher Copyright:
© 2018 The Author(s)
PY - 2018/9/28
Y1 - 2018/9/28
N2 - Axon specification is morphologically reproducible in vitro, whereas dendrite formation differs in vitro and in vivo. Cortical neurons initially develop immature neurites, but in vivo these are eliminated concurrently with the formation of a leading process, the future dendrite. However, the molecular mechanisms underlying these neuronal maturation events remain unclear. Here we show that caveolin-1, a major component of caveolae that are never observed in neurons, regulates in vivo-specific steps of neuronal maturation. Caveolin-1 is predominantly expressed in immature cortical neurons and regulates clathrin-independent endocytosis. In vivo knockdown of caveolin-1 disturbs immature neurite pruning, leading process elongation, and subsequent neuronal migration. Importantly, N-cadherin and L1, which are required for immature neurite formation, undergo caveolin-1-mediated endocytosis to eliminate immature neurites. Collectively, our findings indicate that caveolin-1 regulates N-cadherin and L1 trafficking independent of caveolae, which contributes to spatiotemporally restricted cellular events; immature neurite pruning and leading process elongation during early neuronal maturation.
AB - Axon specification is morphologically reproducible in vitro, whereas dendrite formation differs in vitro and in vivo. Cortical neurons initially develop immature neurites, but in vivo these are eliminated concurrently with the formation of a leading process, the future dendrite. However, the molecular mechanisms underlying these neuronal maturation events remain unclear. Here we show that caveolin-1, a major component of caveolae that are never observed in neurons, regulates in vivo-specific steps of neuronal maturation. Caveolin-1 is predominantly expressed in immature cortical neurons and regulates clathrin-independent endocytosis. In vivo knockdown of caveolin-1 disturbs immature neurite pruning, leading process elongation, and subsequent neuronal migration. Importantly, N-cadherin and L1, which are required for immature neurite formation, undergo caveolin-1-mediated endocytosis to eliminate immature neurites. Collectively, our findings indicate that caveolin-1 regulates N-cadherin and L1 trafficking independent of caveolae, which contributes to spatiotemporally restricted cellular events; immature neurite pruning and leading process elongation during early neuronal maturation.
KW - Cellular Neuroscience
KW - Developmental Neuroscience
KW - Molecular Neuroscience
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U2 - 10.1016/j.isci.2018.08.014
DO - 10.1016/j.isci.2018.08.014
M3 - Article
AN - SCOPUS:85066301335
SN - 2589-0042
VL - 7
SP - 53
EP - 67
JO - iScience
JF - iScience
ER -