LRRTM3 Regulates Excitatory Synapse Development through Alternative Splicing and Neurexin Binding

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http://hdl.handle.net/10138/165449

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Um , J W , Choi , T-Y , Kang , H , Cho , Y S , Choii , G , Uvarov , P , Park , D , Jeong , D , Jeon , S , Lee , D , Kim , H , Lee , S-H , Bae , Y-C , Choi , S-Y , Airaksinen , M S & Ko , J 2016 , ' LRRTM3 Regulates Excitatory Synapse Development through Alternative Splicing and Neurexin Binding ' , Cell Reports , vol. 14 , no. 4 , pp. 808-822 . https://doi.org/10.1016/j.celrep.2015.12.081

Title: LRRTM3 Regulates Excitatory Synapse Development through Alternative Splicing and Neurexin Binding
Author: Um, Ji Won; Choi, Tae-Yong; Kang, Hyeyeon; Cho, Yi Sul; Choii, Gayoung; Uvarov, Pavel; Park, Dongseok; Jeong, Daun; Jeon, Sangmin; Lee, Dongmin; Kim, Hyun; Lee, Seung-Hee; Bae, Yong-Chul; Choi, Se-Young; Airaksinen, Matti S.; Ko, Jaewon
Contributor: University of Helsinki, Medicum
University of Helsinki, Medicum
Date: 2016-02-02
Language: eng
Number of pages: 15
Belongs to series: Cell Reports
ISSN: 2211-1247
URI: http://hdl.handle.net/10138/165449
Abstract: The four members of the LRRTM family (LRRTM1-4) are postsynaptic adhesion molecules essential for excitatory synapse development. They have also been implicated in neuropsychiatric diseases. Here, we focus on LRRTM3, showing that two distinct LRRTM3 variants generated by alternative splicing regulate LRRTM3 interaction with PSD-95, but not its excitatory synapse-promoting activity. Overexpression of either LRRTM3 variant increased excitatory synapse density in dentate gyrus (DG) granule neurons, whereas LRRTM3 knockdown decreased it. LRRTM3 also controlled activity-regulated AMPA receptor surface expression in an alternative splicing-dependent manner. Furthermore, Lrrtm3-knockout mice displayed specific alterations in excitatory synapse density, excitatory synaptic transmission and excitability in DG granule neurons but not in CA1 pyramidal neurons. Lastly, LRRTM3 required only specific splice variants of presynaptic neurexins for their synaptogenic activity. Collectively, our data highlight alternative splicing and differential presynaptic ligand utilization in the regulation of LRRTMs, revealing key regulatory mechanisms for excitatory synapse development.
Subject: REPEAT TRANSMEMBRANE PROTEINS
ADHESION MOLECULES
TYROSINE PHOSPHATASES
PTP-SIGMA
RECEPTOR
NEUROLIGINS
AMPA
COMPLEX
FAMILY
ORGANIZATION
3111 Biomedicine
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