Increased excitatory synaptic transmission of dentate granule neurons in mice lacking PSD-95-interacting adhesion molecule Neph2/Kirrel3 during the early postnatal period

Junyeop D. Roh, Su Yeon Choi, Yi Sul Cho, Tae Yong Choi, Jong Sil Park, Tyler Cutforth, Woosuk Chung, Hanwool Park, Dongsoo Lee, Myeong Heui Kim, Yeunkum Lee, Seojung Mo, Jeong Seop Rhee, Hyun Kim, Jaewon Ko, Se Young Choi, Yong Chul Bae, Kang Shen, Eunjoon Kim, Kihoon Han

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Copy number variants and point mutations of NEPH2 (also called KIRREL3) gene encoding an immunoglobulin (Ig) superfamily adhesion molecule have been linked to autism spectrum disorders, intellectual disability and neurocognitive delay associated with Jacobsen syndrome, but the physiological roles of Neph2 in the mammalian brain remain largely unknown. Neph2 is highly expressed in the dentate granule (DG) neurons of the hippocampus and is localized in both dendrites and axons. It was recently shown that Neph2 is required for the formation of mossy fiber filopodia, the axon terminal structure of DG neurons forming synapses with GABAergic neurons of CA3. In contrast, however, it is unknown whether Neph2 also has any roles in the postsynaptic compartments of DG neurons. We here report that, through its C-terminal PDZ domain-binding motif, Neph2 directly interacts with postsynaptic density (PSD)-95, an abundant excitatory postsynaptic scaffolding protein. Moreover, Neph2 protein is detected in the brain PSD fraction and interacts with PSD-95 in synaptosomal lysates. Functionally, loss of Neph2 in mice leads to age-specific defects in the synaptic connectivity of DG neurons. Specifically, Neph2−/− mice show significantly increased spontaneous excitatory synaptic events in DG neurons at postnatal week 2 when the endogenous Neph2 protein expression peaks, but show normal excitatory synaptic transmission at postnatal week 3. The evoked excitatory synaptic transmission and synaptic plasticity of medial perforant pathway (MPP)-DG synapses are also normal in Neph2−/− mice at postnatal week 3, further confirming the age-specific synaptic defects. Together, our results provide some evidence for the postsynaptic function of Neph2 in DG neurons during the early postnatal period, which might be implicated in neurodevelopmental and cognitive disorders caused by NEPH2 mutations.

Original languageEnglish
Article number81
JournalFrontiers in Molecular Neuroscience
Volume10
DOIs
Publication statusPublished - 2017 Mar 22

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Post-Synaptic Density
Synaptic Transmission
Neurons
Synapses
Jacobsen Distal 11q Deletion Syndrome
Perforant Pathway
PDZ Domains
GABAergic Neurons
Immunoglobulin Genes
Proteins
Pseudopodia
Neuronal Plasticity
Presynaptic Terminals
Brain
Dendrites
Point Mutation
Intellectual Disability
Axons
Hippocampus
Mutation

Keywords

  • Dentate granule neuron
  • Excitatory synapse
  • Kirrel3
  • Neph2
  • PSD-95

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience

Cite this

Increased excitatory synaptic transmission of dentate granule neurons in mice lacking PSD-95-interacting adhesion molecule Neph2/Kirrel3 during the early postnatal period. / Roh, Junyeop D.; Choi, Su Yeon; Cho, Yi Sul; Choi, Tae Yong; Park, Jong Sil; Cutforth, Tyler; Chung, Woosuk; Park, Hanwool; Lee, Dongsoo; Kim, Myeong Heui; Lee, Yeunkum; Mo, Seojung; Rhee, Jeong Seop; Kim, Hyun; Ko, Jaewon; Choi, Se Young; Bae, Yong Chul; Shen, Kang; Kim, Eunjoon; Han, Kihoon.

In: Frontiers in Molecular Neuroscience, Vol. 10, 81, 22.03.2017.

Research output: Contribution to journalArticle

Roh, JD, Choi, SY, Cho, YS, Choi, TY, Park, JS, Cutforth, T, Chung, W, Park, H, Lee, D, Kim, MH, Lee, Y, Mo, S, Rhee, JS, Kim, H, Ko, J, Choi, SY, Bae, YC, Shen, K, Kim, E & Han, K 2017, 'Increased excitatory synaptic transmission of dentate granule neurons in mice lacking PSD-95-interacting adhesion molecule Neph2/Kirrel3 during the early postnatal period', Frontiers in Molecular Neuroscience, vol. 10, 81. https://doi.org/10.3389/fnmol.2017.00081
Roh, Junyeop D. ; Choi, Su Yeon ; Cho, Yi Sul ; Choi, Tae Yong ; Park, Jong Sil ; Cutforth, Tyler ; Chung, Woosuk ; Park, Hanwool ; Lee, Dongsoo ; Kim, Myeong Heui ; Lee, Yeunkum ; Mo, Seojung ; Rhee, Jeong Seop ; Kim, Hyun ; Ko, Jaewon ; Choi, Se Young ; Bae, Yong Chul ; Shen, Kang ; Kim, Eunjoon ; Han, Kihoon. / Increased excitatory synaptic transmission of dentate granule neurons in mice lacking PSD-95-interacting adhesion molecule Neph2/Kirrel3 during the early postnatal period. In: Frontiers in Molecular Neuroscience. 2017 ; Vol. 10.
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AU - Cho, Yi Sul

AU - Choi, Tae Yong

AU - Park, Jong Sil

AU - Cutforth, Tyler

AU - Chung, Woosuk

AU - Park, Hanwool

AU - Lee, Dongsoo

AU - Kim, Myeong Heui

AU - Lee, Yeunkum

AU - Mo, Seojung

AU - Rhee, Jeong Seop

AU - Kim, Hyun

AU - Ko, Jaewon

AU - Choi, Se Young

AU - Bae, Yong Chul

AU - Shen, Kang

AU - Kim, Eunjoon

AU - Han, Kihoon

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