An Essential Role of Fyn in the Modulation of Metabotropic Glutamate Receptor 1 in Neurons

Jin, Dao Zhong; Mao, Li; Wang, John Q.

doi:10.1523/eneuro.0096-17.2017

Cited by 22 publications

(25 citation statements)

References 62 publications

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“…The brown module contained PiSCES that decreased after both upscaling and downscaling, which could suggest a PIN that dissociates after prolonged changes in activity, regardless of whether activity is increased or decreased. This module included several PiSCES containing the kinse Fyn, which phosphorylates both NMDAR2B and mGluR1 (Jin et al, 2017;Nakazawa et al, 2001;Yang and Leonard, 2001)), and mGluR5_Fyn co-association was significantly reduced following TTX treatment (Fig. 2D).…”

Section: Upscaling and Downscaling Induce Bidirectional And Unidirectmentioning

confidence: 99%

Homeostatic Plasticity Requires Remodeling of the Homer-Shank Interactome

We¹,

Speed²,

Jd³

et al. 2020

Preprint

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Neurons maintain constant levels of excitability using homeostatic scaling, which adjusts relative synaptic strength in response to large changes in overall activity. While previous studies have catalogued the transcriptomic and proteomic changes associated with scaling, the resulting alterations in synaptic protein interaction networks (PINs) are less well understood. Here, we monitor a glutamatergic synapse PIN composed of 380 binary interactions among 21 protein members to identify protein complexes altered by synaptic scaling. In cultured cortical neurons, we observe widespread bidirectional PIN alterations with up-versus downscaling. In the barrel cortex, the PIN response to 48 hours of sensory deprivation exhibits characteristics of both upscaling and downscaling, consistent with emerging models of excitatory/inhibitory balance in cortical plasticity. Mice lacking Homer1 or Shank3B do not undergo normal PIN rearrangements, suggesting that these Autism Spectrum Disorder (ASD)-linked proteins serve as structural hubs for synaptic homeostasis. Our approach demonstrates how previously identified RNA and protein-level changes induced during homeostatic scaling translate into functional PIN alterations.

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Section: Upscaling and Downscaling Induce Bidirectional And Unidirectmentioning

confidence: 99%

Homeostatic Plasticity Requires Remodeling of the Homer-Shank Interactome

We¹,

Speed²,

Jd³

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…Fyn was also shown to promote ERK1/2 phosphorylation in oligodendrocytes (Peckham et al, 2016), and NfkB signaling in microglia (Panicker et al, 2015); both signaling cascades have been linked to alcohol use (Crews et al, 2011;Ron et al, 2016). Finally, Fyn was reported to phosphorylate the metabotropic glutamate receptor 1 (mGluR1) (Jin et al, 2017)…”

Section: Discussionmentioning

confidence: 99%

cAMP-Fyn signaling in the dorsomedial striatum direct pathway drives excessive alcohol use

Ehinger

Morisot

Phamluong

et al. 2020

Preprint

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Fyn kinase in the dorsomedial striatum (DMS) of rodents plays a central role in mechanisms underlying excessive alcohol intake. The DMS is comprised mostly of medium spiny neurons (MSNs) that are divided into dopamine D1 receptor expressing neurons (dMSNs), and dopamine D2 receptor expressing neurons (iMSNs). Here, we examined the cell-type specificity of Fyn's actions on the development of alcohol use. First, we knocked down Fyn selectively in DMS dMSNs or iMSNs of mice and measured the level of alcohol consumption. We found that downregulation of Fyn in dMSNs, but not in iMSNs, reduces excessive alcohol but not saccharin intake and preference. D1Rs are coupled to Gαs/olf, which activate cAMP signaling. To examine whether Fyn's actions are mediated through cAMP signaling, DMS dMSNs were infected with GαsDREADD, and the activation of Fyn signaling was measured following CNO treatment. We found that remote stimulation of cAMP signaling in DMS dMSNs activates Fyn and promotes the phosphorylation of the Fyn substrate, GluN2B. Next, we tested whether remote activation of GαsDREADD in DMS dMSNs or iMSNs alters alcohol intake, and observed that CNO-dependent activation of GαsDREADD in DMS dMSNs but not iMSNs increases alcohol but not saccharin intake and preference. Finally, we examined the contribution of Fyn to GαsDREADD-dependent increase in alcohol intake, and found that systemic administration of the Fyn inhibitor, AZD0503 blocks GαsDREADD-dependent increase in alcohol consumption.Our results suggest that the cAMP-Fyn axis in the DMS dMSNs is a molecular transducer of mechanisms underlying the development of excessive alcohol consumption.

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“…Indeed, Src inhibition reduces mGluR1-activated inward currents in hippocampal CA3 pyramidal neurons [41] and dampens mGluR1-dependent activation of ERK2 [46]. mGluR1 is also a target of Fyn, which is directly bound to its intracellular C terminal domain [47]. Fyn-mediated phosphorylation of mGluR1a is constitutively active and facilitates its surface expression and function in rat cerebellar neurons [47].…”

Section: Protein Kinases-dependent Regulation Of Mgluri: Focus On Tyrmentioning

confidence: 99%

Insights on the Functional Interaction between Group 1 Metabotropic Glutamate Receptors (mGluRI) and ErbB Receptors

Ledonne

Mercuri

2020

IJMS

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It is well-appreciated that phosphorylation is an essential post-translational mechanism of regulation for several proteins, including group 1 metabotropic glutamate receptors (mGluRI), mGluR1, and mGluR5 subtypes. While contributions of various serine/threonine protein kinases on mGluRI modulation have been recognized, the functional role of tyrosine kinases (TKs) is less acknowledged. Here, while describing current evidence supporting that mGluRI are targets of TKs, we mainly focus on the modulatory roles of the ErbB tyrosine kinases receptors—activated by the neurotrophic factors neuregulins (NRGs)—on mGluRI function. Available evidence suggests that mGluRI activity is tightly dependent on ErbB signaling, and that ErbB’s modulation profoundly influences mGluRI-dependent effects on neurotransmission, neuronal excitability, synaptic plasticity, and learning and memory processes.

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An Essential Role of Fyn in the Modulation of Metabotropic Glutamate Receptor 1 in Neurons

Cited by 22 publications

References 62 publications

Homeostatic Plasticity Requires Remodeling of the Homer-Shank Interactome

Homeostatic Plasticity Requires Remodeling of the Homer-Shank Interactome

cAMP-Fyn signaling in the dorsomedial striatum direct pathway drives excessive alcohol use

Insights on the Functional Interaction between Group 1 Metabotropic Glutamate Receptors (mGluRI) and ErbB Receptors

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