TY - JOUR
T1 - Presynaptically Released Cbln1 Induces Dynamic Axonal Structural Changes by Interacting with GluD2 during Cerebellar Synapse Formation
AU - Ito-Ishida, Aya
AU - Miyazaki, Taisuke
AU - Miura, Eriko
AU - Matsuda, Keiko
AU - Watanabe, Masahiko
AU - Yuzaki, Michisuke
AU - Okabe, Shigeo
N1 - Funding Information:
We thank Dr. Morgan (St. Jude Children’s Research Hospital) for cbln1-null mice, Dr. Miyazaki (Osaka University) for pCAGGS expression vector, Dr. Scheiffele (University of Basel) for anti-Nrx antibody and Nrx isoform cDNAs, Dr. Goda (RIKEN Brain Science Institue) for synaptophysin-encoding cDNA, Dr. Nakanishi (Osaka Bioscience Institute, Osaka, Japan) for TNT cDNA, and Dr. Kohda and Dr. Kakegawa (Keio University) for providing Sindbis virus. We thank Dr. Honda (Keio University) for advice on electroporation, and Mr. Obashi (University of Tokyo) for advice on live imaging. This work was supported by Grants-in-Aid for Scientific Research (18200025, 20019013, 21220008, and 22650070 [to S.O.]; 40365226 [to M.Y.]), the Grant-in-Aid for Scientific Research on Innovative Areas (23110002 [to M.Y.]), Research Fellowship for Young Scientists (to A.I.-I.), the Strategic Research Program for Brain Sciences (Development of Biomarker Candidates for Social Behavior), and the Global Centers of Excellence Program (Integrative Life Science Based on the Study of Biosignaling Mechanisms) from Ministry of Education, Culture, Sports, Science and Technology, Japan, and by Core Research for Evolutional Science and Technology from the Japanese Science and Technology Agency (to M.Y.).
PY - 2012/11/8
Y1 - 2012/11/8
N2 - Differentiation of pre- and postsynaptic sites is coordinated by reciprocal interaction across synaptic clefts. At parallel fiber (PF)-Purkinje cell (PC) synapses, dendritic spines are autonomously formed without PF influence. However, little is known about how presynaptic structural changes are induced and how they lead to differentiation of mature synapses. Here, we show that Cbln1 released from PFs induces dynamic structural changes in PFs by a mechanism that depends on postsynaptic glutamate receptor delta2 (GluD2) and presynaptic neurexin (Nrx). Time-lapse imaging in organotypic culture and ultrastructural analyses in vivo revealed that Nrx-Cbln1-GluD2 signaling induces PF protrusions that often formed circular structures and encapsulated PC spines. Such structural changes in PFs were associated with the accumulation of synaptic vesicles and GluD2, leading to formation of mature synapses. Thus, PF protrusions triggered by Nrx-Cbln1-GluD2 signaling may promote bidirectional maturation of PF-PC synapses by a positive feedback mechanism
AB - Differentiation of pre- and postsynaptic sites is coordinated by reciprocal interaction across synaptic clefts. At parallel fiber (PF)-Purkinje cell (PC) synapses, dendritic spines are autonomously formed without PF influence. However, little is known about how presynaptic structural changes are induced and how they lead to differentiation of mature synapses. Here, we show that Cbln1 released from PFs induces dynamic structural changes in PFs by a mechanism that depends on postsynaptic glutamate receptor delta2 (GluD2) and presynaptic neurexin (Nrx). Time-lapse imaging in organotypic culture and ultrastructural analyses in vivo revealed that Nrx-Cbln1-GluD2 signaling induces PF protrusions that often formed circular structures and encapsulated PC spines. Such structural changes in PFs were associated with the accumulation of synaptic vesicles and GluD2, leading to formation of mature synapses. Thus, PF protrusions triggered by Nrx-Cbln1-GluD2 signaling may promote bidirectional maturation of PF-PC synapses by a positive feedback mechanism
UR - http://www.scopus.com/inward/record.url?scp=84868650972&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84868650972&partnerID=8YFLogxK
U2 - 10.1016/j.neuron.2012.07.027
DO - 10.1016/j.neuron.2012.07.027
M3 - Article
C2 - 23141067
AN - SCOPUS:84868650972
SN - 0896-6273
VL - 76
SP - 549
EP - 564
JO - Neuron
JF - Neuron
IS - 3
ER -