AMPAR Auxiliary Protein SHISA6 Facilitates Purkinje Cell Synaptic Excitability and Procedural Memory Formation

Saša Peter; Bastiaan H.A. Urbanus; Remco V. Klaassen; Bin Wu; Henk Jan Boele; Sameha Azizi; Johan A. Slotman; Adriaan B. Houtsmuller; Martijn Schonewille; Freek E. Hoebeek; Sabine Spijker; August B. Smit; Chris I. De Zeeuw

doi:10.1016/j.celrep.2020.03.079

AMPAR Auxiliary Protein SHISA6 Facilitates Purkinje Cell Synaptic Excitability and Procedural Memory Formation

Saša Peter
, Bastiaan H.A. Urbanus
, Remco V. Klaassen
, Bin Wu
, Henk Jan Boele
, Sameha Azizi
, Johan A. Slotman
, Adriaan B. Houtsmuller
, Martijn Schonewille
, Freek E. Hoebeek
, Sabine Spijker
, August B. Smit^*
, Chris I. De Zeeuw

^*Corresponding author for this work

Research output: Contribution to Journal › Article › Academic › peer-review

Abstract

The majority of excitatory postsynaptic currents in the brain are gated through AMPA-type glutamate receptors, the kinetics and trafficking of which can be modulated by auxiliary proteins. It remains to be elucidated whether and how auxiliary proteins can modulate synaptic function to contribute to procedural memory formation. In this study, we report that the AMPA-type glutamate receptor (AMPAR) auxiliary protein SHISA6 (CKAMP52) is expressed in cerebellar Purkinje cells, where it co-localizes with GluA2-containing AMPARs. The absence of SHISA6 in Purkinje cells results in severe impairments in the adaptation of the vestibulo-ocular reflex and eyeblink conditioning. The physiological abnormalities include decreased presence of AMPARs in synaptosomes, impaired excitatory transmission, increased deactivation of AMPA receptors, and reduced induction of long-term potentiation at Purkinje cell synapses. Our data indicate that Purkinje cells require SHISA6-dependent modification of AMPAR function in order to facilitate cerebellar, procedural memory formation.

Original language	English
Article number	107515
Pages (from-to)	1-22
Number of pages	22
Journal	Cell Reports
Volume	31
Issue number	2
Early online date	14 Apr 2020
DOIs	https://doi.org/10.1016/j.celrep.2020.03.079
Publication status	Published - 14 Apr 2020

Funding

We would like to express our gratitude for excellent technical assistance by Elize Haasdijk, Mandy Rutteman, and Laura Post. Financial support for C.I.D.Z. was provided by the Netherlands Organisation for Scientific Research (NWO-ALW), the Dutch Organization for Medical Sciences (ZonMW), ERC-adv , ERC-POC , EU-LISTEN, Medical NeuroDelta , and INTENSE (NWO-LSH). R.V.K. was funded by NWO-ALW grant ( ALW2PJ/12048 ), S.S. by an NWO VICI grant ( ALW-Vici 016.150.673/865.14.002 ), and M.S. by an ERC-StG grant ( 680235 ).

Funders	Funder number
Dutch Organization for Medical Sciences
ERC-PoC
ERC-StG
ERC-adv
EU-LISTEN
INTENSE
Medical NeuroDelta
NWO-ALW
NWO-LSH	ALW2PJ/12048
Horizon 2020 Framework Programme	680235
ZonMw
Nederlandse Organisatie voor Wetenschappelijk Onderzoek	ALW-Vici 016.150.673/865.14.002

Keywords

AMPAR kinetics
auxiliary subunit
cerebellum
long-term depression
procedural memory
synapse

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10.1016/j.celrep.2020.03.079

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Peter, S., Urbanus, B. H. A., Klaassen, R. V., Wu, B., Boele, H. J., Azizi, S., Slotman, J. A., Houtsmuller, A. B., Schonewille, M., Hoebeek, F. E., Spijker, S., Smit, A. B., & De Zeeuw, C. I. (2020). AMPAR Auxiliary Protein SHISA6 Facilitates Purkinje Cell Synaptic Excitability and Procedural Memory Formation. Cell Reports, 31(2), 1-22. Article 107515. https://doi.org/10.1016/j.celrep.2020.03.079

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title = "AMPAR Auxiliary Protein SHISA6 Facilitates Purkinje Cell Synaptic Excitability and Procedural Memory Formation",

abstract = "The majority of excitatory postsynaptic currents in the brain are gated through AMPA-type glutamate receptors, the kinetics and trafficking of which can be modulated by auxiliary proteins. It remains to be elucidated whether and how auxiliary proteins can modulate synaptic function to contribute to procedural memory formation. In this study, we report that the AMPA-type glutamate receptor (AMPAR) auxiliary protein SHISA6 (CKAMP52) is expressed in cerebellar Purkinje cells, where it co-localizes with GluA2-containing AMPARs. The absence of SHISA6 in Purkinje cells results in severe impairments in the adaptation of the vestibulo-ocular reflex and eyeblink conditioning. The physiological abnormalities include decreased presence of AMPARs in synaptosomes, impaired excitatory transmission, increased deactivation of AMPA receptors, and reduced induction of long-term potentiation at Purkinje cell synapses. Our data indicate that Purkinje cells require SHISA6-dependent modification of AMPAR function in order to facilitate cerebellar, procedural memory formation.",

keywords = "AMPAR kinetics, auxiliary subunit, cerebellum, long-term depression, procedural memory, synapse",

author = "Sa{\v s}a Peter and Urbanus, \{Bastiaan H.A.\} and Klaassen, \{Remco V.\} and Bin Wu and Boele, \{Henk Jan\} and Sameha Azizi and Slotman, \{Johan A.\} and Houtsmuller, \{Adriaan B.\} and Martijn Schonewille and Hoebeek, \{Freek E.\} and Sabine Spijker and Smit, \{August B.\} and \{De Zeeuw\}, \{Chris I.\}",

year = "2020",

month = apr,

day = "14",

doi = "10.1016/j.celrep.2020.03.079",

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Peter, S, Urbanus, BHA, Klaassen, RV, Wu, B, Boele, HJ, Azizi, S, Slotman, JA, Houtsmuller, AB, Schonewille, M, Hoebeek, FE, Spijker, S , Smit, AB & De Zeeuw, CI 2020, 'AMPAR Auxiliary Protein SHISA6 Facilitates Purkinje Cell Synaptic Excitability and Procedural Memory Formation', Cell Reports, vol. 31, no. 2, 107515, pp. 1-22. https://doi.org/10.1016/j.celrep.2020.03.079

TY - JOUR

T1 - AMPAR Auxiliary Protein SHISA6 Facilitates Purkinje Cell Synaptic Excitability and Procedural Memory Formation

AU - Peter, Saša

AU - Urbanus, Bastiaan H.A.

AU - Klaassen, Remco V.

AU - Wu, Bin

AU - Boele, Henk Jan

AU - Azizi, Sameha

AU - Slotman, Johan A.

AU - Houtsmuller, Adriaan B.

AU - Schonewille, Martijn

AU - Hoebeek, Freek E.

AU - Spijker, Sabine

AU - Smit, August B.

AU - De Zeeuw, Chris I.

PY - 2020/4/14

Y1 - 2020/4/14

N2 - The majority of excitatory postsynaptic currents in the brain are gated through AMPA-type glutamate receptors, the kinetics and trafficking of which can be modulated by auxiliary proteins. It remains to be elucidated whether and how auxiliary proteins can modulate synaptic function to contribute to procedural memory formation. In this study, we report that the AMPA-type glutamate receptor (AMPAR) auxiliary protein SHISA6 (CKAMP52) is expressed in cerebellar Purkinje cells, where it co-localizes with GluA2-containing AMPARs. The absence of SHISA6 in Purkinje cells results in severe impairments in the adaptation of the vestibulo-ocular reflex and eyeblink conditioning. The physiological abnormalities include decreased presence of AMPARs in synaptosomes, impaired excitatory transmission, increased deactivation of AMPA receptors, and reduced induction of long-term potentiation at Purkinje cell synapses. Our data indicate that Purkinje cells require SHISA6-dependent modification of AMPAR function in order to facilitate cerebellar, procedural memory formation.

AB - The majority of excitatory postsynaptic currents in the brain are gated through AMPA-type glutamate receptors, the kinetics and trafficking of which can be modulated by auxiliary proteins. It remains to be elucidated whether and how auxiliary proteins can modulate synaptic function to contribute to procedural memory formation. In this study, we report that the AMPA-type glutamate receptor (AMPAR) auxiliary protein SHISA6 (CKAMP52) is expressed in cerebellar Purkinje cells, where it co-localizes with GluA2-containing AMPARs. The absence of SHISA6 in Purkinje cells results in severe impairments in the adaptation of the vestibulo-ocular reflex and eyeblink conditioning. The physiological abnormalities include decreased presence of AMPARs in synaptosomes, impaired excitatory transmission, increased deactivation of AMPA receptors, and reduced induction of long-term potentiation at Purkinje cell synapses. Our data indicate that Purkinje cells require SHISA6-dependent modification of AMPAR function in order to facilitate cerebellar, procedural memory formation.

KW - AMPAR kinetics

KW - auxiliary subunit

KW - cerebellum

KW - long-term depression

KW - procedural memory

KW - synapse

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VL - 31

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JO - Cell Reports

JF - Cell Reports

IS - 2

M1 - 107515

ER -

AMPAR Auxiliary Protein SHISA6 Facilitates Purkinje Cell Synaptic Excitability and Procedural Memory Formation

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