Molecular mechanism of parallel fiber-Purkinje cell synapse formation

The cerebellum receives two excitatory afferents, the climbing fiber (CF) and the mossy fiber-parallel fiber (PF) pathway, both converging onto Purkinje cells (PCs) that are the sole neurons sending outputs from the cerebellar cortex. Glutamate receptor δ2 (GluRδ2) is expressed selectively in cerebe...

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Main Authors:	Mishina, Masayoshi, Uemura, Takeshi, Yasumura, Misato, Yoshida, Tomoyuki
Format:	Online
Language:	English
Published:	Frontiers Media S.A. 2012
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3505014/

id	pubmed-3505014
recordtype	oai_dc
spelling	pubmed-35050142012-11-27 Molecular mechanism of parallel fiber-Purkinje cell synapse formation Mishina, Masayoshi Uemura, Takeshi Yasumura, Misato Yoshida, Tomoyuki Neuroscience The cerebellum receives two excitatory afferents, the climbing fiber (CF) and the mossy fiber-parallel fiber (PF) pathway, both converging onto Purkinje cells (PCs) that are the sole neurons sending outputs from the cerebellar cortex. Glutamate receptor δ2 (GluRδ2) is expressed selectively in cerebellar PCs and localized exclusively at the PF-PC synapses. We found that a significant number of PC spines lack synaptic contacts with PF terminals and some of residual PF-PC synapses show mismatching between pre- and postsynaptic specializations in conventional and conditional GluRδ2 knockout mice. Studies with mutant mice revealed that in addition to PF-PC synapse formation, GluRδ2 is essential for synaptic plasticity, motor learning, and the restriction of CF territory. GluRδ2 regulates synapse formation through the amino-terminal domain, while the control of synaptic plasticity, motor learning, and CF territory is mediated through the carboxyl-terminal domain. Thus, GluRδ2 is the molecule that bridges synapse formation and motor learning. We found that the trans-synaptic interaction of postsynaptic GluRδ2 and presynaptic neurexins (NRXNs) through cerebellin 1 (Cbln1) mediates PF-PC synapse formation. The synaptogenic triad is composed of one molecule of tetrameric GluRδ2, two molecules of hexameric Cbln1 and four molecules of monomeric NRXN. Thus, GluRδ2 triggers synapse formation by clustering four NRXNs. These findings provide a molecular insight into the mechanism of synapse formation in the brain. Frontiers Media S.A. 2012-11-23 /pmc/articles/PMC3505014/ /pubmed/23189042 http://dx.doi.org/10.3389/fncir.2012.00090 Text en Copyright © 2012 Mishina, Uemura, Yasumura and Yoshida. http://www.frontiersin.org/licenseagreement This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and subject to any copyright notices concerning any third-party graphics etc.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Mishina, Masayoshi Uemura, Takeshi Yasumura, Misato Yoshida, Tomoyuki
spellingShingle	Mishina, Masayoshi Uemura, Takeshi Yasumura, Misato Yoshida, Tomoyuki Molecular mechanism of parallel fiber-Purkinje cell synapse formation
author_facet	Mishina, Masayoshi Uemura, Takeshi Yasumura, Misato Yoshida, Tomoyuki
author_sort	Mishina, Masayoshi
title	Molecular mechanism of parallel fiber-Purkinje cell synapse formation
title_short	Molecular mechanism of parallel fiber-Purkinje cell synapse formation
title_full	Molecular mechanism of parallel fiber-Purkinje cell synapse formation
title_fullStr	Molecular mechanism of parallel fiber-Purkinje cell synapse formation
title_full_unstemmed	Molecular mechanism of parallel fiber-Purkinje cell synapse formation
title_sort	molecular mechanism of parallel fiber-purkinje cell synapse formation
description	The cerebellum receives two excitatory afferents, the climbing fiber (CF) and the mossy fiber-parallel fiber (PF) pathway, both converging onto Purkinje cells (PCs) that are the sole neurons sending outputs from the cerebellar cortex. Glutamate receptor δ2 (GluRδ2) is expressed selectively in cerebellar PCs and localized exclusively at the PF-PC synapses. We found that a significant number of PC spines lack synaptic contacts with PF terminals and some of residual PF-PC synapses show mismatching between pre- and postsynaptic specializations in conventional and conditional GluRδ2 knockout mice. Studies with mutant mice revealed that in addition to PF-PC synapse formation, GluRδ2 is essential for synaptic plasticity, motor learning, and the restriction of CF territory. GluRδ2 regulates synapse formation through the amino-terminal domain, while the control of synaptic plasticity, motor learning, and CF territory is mediated through the carboxyl-terminal domain. Thus, GluRδ2 is the molecule that bridges synapse formation and motor learning. We found that the trans-synaptic interaction of postsynaptic GluRδ2 and presynaptic neurexins (NRXNs) through cerebellin 1 (Cbln1) mediates PF-PC synapse formation. The synaptogenic triad is composed of one molecule of tetrameric GluRδ2, two molecules of hexameric Cbln1 and four molecules of monomeric NRXN. Thus, GluRδ2 triggers synapse formation by clustering four NRXNs. These findings provide a molecular insight into the mechanism of synapse formation in the brain.
publisher	Frontiers Media S.A.
publishDate	2012
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3505014/
_version_	1611934900982644736

Molecular mechanism of parallel fiber-Purkinje cell synapse formation

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