Stargazin regulates AMPA receptor trafficking through adaptor protein complexes during long-term depression

Matsuda, Shinji; Kakegawa, Wataru; Budisantoso, Timotheus; Nomura, Toshihiro; Kohda, Kazuhisa; Yuzaki, Michisuke

doi:10.1038/ncomms3759

Cited by 67 publications

(103 citation statements)

References 46 publications

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“…Other possibilities include a site-specific phosphorylation code and/or a temporal sequence in serine phosphorylation. The latter is an attractive model, supported by our findings that the time-course for phosphorylation of S239/S249 and S228 in STG is different in response to chronic inactivity, and is consistent with the finding that different phosphorylation sites regulate the binding of STG to other proteins (Matsuda et al, 2013). In the future, it will be interesting to test whether phosphorylation of specific serine residues distinguishes between the two fundamentally different forms of synaptic plasticity.…”

Section: Discussionsupporting

confidence: 88%

A Role for Stargazin in Experience-Dependent Plasticity

et al. 2014

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Summary During development neurons are constantly refining their connections in response to changes in activity. Experience-dependent plasticity is a key form of synaptic plasticity, involving changes in α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) accumulation at synapses. Here we report a critical role for the AMPAR auxiliary subunit, stargazin, in this plasticity. We show that stargazin is functional at the retinogeniculate synapse and that in the absence of stargazin, the refinement of the retinogeniculate synapse is specifically disrupted during the experience-dependent phase. Importantly, we found that stargazin expression and phosphorylation increased with visual deprivation, and led to reduced AMPAR rectification at the retinogeniculate synapse. To test whether stargazin may play a role in homeostatic plasticity, we turned to cultured neurons and found that stargazin phosphorylation is essential for synaptic scaling. Overall, our data reveal an important new role of stargazin in regulating AMPAR abundance and composition at glutamatergic synapses during homeostatic and experience-dependent plasticity.

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Section: Discussionsupporting

confidence: 88%

A Role for Stargazin in Experience-Dependent Plasticity

et al. 2014

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“…AP-3A, which associates indirectly with AMPAR through μ3A binding to TARPs, has been implicated in the sorting and trafficking of glutamate receptors (Matsuda et al, 2013), suggesting that transcriptional upregulation of μ3A might play a critical role in synaptic scaling. As expected, immunohistochemistry localized μ3 to a number of endosomal compartments within pyramidal neurons (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Next, we asked whether μ3A must interact with the AP-3 complex in order to traffic GluA2 to RE. The μ3A subunit interacts with the AP-3A complex through its N terminal domain, and interacts with TARPS (and thus AMPAR) through its C terminal domain (Aguilar et al, 1997; Mardones et al, 2013; Matsuda et al, 2013). Because TTX selectively increases μ3A without increasing expression of the other AP-3 subunits, and OE of μ3A alone is sufficient to recruit AMPAR to RE (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Although none of these complexes were previously known to have activity-regulated expression, several of them have been implicated in basal sorting and trafficking of Glutamate receptors (Margeta et al, 2009; Kastning et al, 2007; Lee et al, 2002). In particular, μ3A and μ4 can bind AMPAR indirectly through interactions with TARPS (Matsuda et al, 2008; Matsuda et al, 2013), and this interaction is important for dendritic trafficking of AMPAR (Matsuda et al, 2008) and for NMDA-induced trafficking of internalized AMPAR from early endosomes to lysosomes (AP-3, Matsuda et al, 2013). These considerations suggest that μ3A could contribute to the regulated trafficking of AMPAR that underlies synaptic scaling up (Kennedy and Ehlers, 2006; Turrigiano, 2008).…”

Section: Introductionmentioning

confidence: 99%

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Upregulation of μ3A Drives Homeostatic Plasticity by Rerouting AMPAR into the Recycling Endosomal Pathway

et al. 2016

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SUMMARY Synaptic scaling is a form of homeostatic plasticity driven by transcription-dependent changes in AMPA-type glutamate receptor (AMPAR) trafficking. To uncover the pathways involved we performed a cell-type specific screen for transcripts persistently altered during scaling, which identified the μ subunit (μ3A) of the adaptor protein complex AP-3A. Synaptic scaling increased μ3A (but not other AP-3 subunits) in pyramidal neurons, and redistributed dendritic μ3A and AMPAR to recycling endosomes (REs). Knockdown of μ3A prevented synaptic scaling and this redistribution, while overexpression (OE) of full-length or truncated μ3A (that cannot interact with the AP-3A complex) was sufficient to drive AMPAR to REs. Finally, OE of μ3A acted synergistically with GRIP1 to recruit AMPAR to the dendritic membrane. These data suggest that excess μ3A acts independently of the AP-3A complex to re-route AMPAR to RE, generating a reservoir of receptors essential for the regulated recruitment to the synaptic membrane during scaling up.

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“…The encoding gene is targeted in the stargazer mouse (Letts et al 1998) and has been shown to be a modulator of a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors at postsynaptic membranes (Tomita et al 2005;Bats et al 2007;Matsuda et al 2013). Seven different splice isoforms of the g subunit have been identified in neurons (Klugbaueret al 2000;Chen et al 2007), and, although when heterologously expressed with Ca V 2.1 (P/ Q-type) channels, they exerted effects on channel physiology (Rousset et al 2001), it is unclear whether they are genuine accessory subunits of the neuronal calcium channel complex in vivo (Ahlijanian et al 1990;McEnery et al 1991;Witcher et al 1994;Martin-Moutot et al 1995).…”

Section: Calcium Channel Structurementioning

confidence: 99%

The Role of Calcium Channels in Epilepsy

Rajakulendran

Hanna

2016

Cold Spring Harb Perspect Med

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A central theme in the quest to unravel the genetic basis of epilepsy has been the effort to elucidate the roles played by inherited defects in ion channels. The ubiquitous expression of voltage-gated calcium channels (VGCCs) throughout the central nervous system (CNS), along with their involvement in fundamental processes, such as neuronal excitability and synaptic transmission, has made them attractive candidates. Recent insights provided by the identification of mutations in the P/Q-type calcium channel in humans and rodents with epilepsy and the finding of thalamic T-type calcium channel dysfunction in the absence of seizures have raised expectations of a causal role of calcium channels in the polygenic inheritance of idiopathic epilepsy. In this review, we consider how genetic variation in neuronal VGCCs may influence the development of epilepsy.

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Stargazin regulates AMPA receptor trafficking through adaptor protein complexes during long-term depression

Cited by 67 publications

References 46 publications

A Role for Stargazin in Experience-Dependent Plasticity

A Role for Stargazin in Experience-Dependent Plasticity

Upregulation of μ3A Drives Homeostatic Plasticity by Rerouting AMPAR into the Recycling Endosomal Pathway

The Role of Calcium Channels in Epilepsy

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