Src family kinases: modulators of neurotransmitter receptor function and behavior

doi:10.1016/j.tins.2011.09.005

Trends in Neurosciences

Volume 34, Issue 12, December 2011, Pages 629-637

https://doi.org/10.1016/j.tins.2011.09.005 Get rights and content

Src family kinases (SFKs) are non-receptor-type protein tyrosine kinases that were originally identified as the products of proto-oncogenes and were subsequently implicated in the regulation of cell proliferation and differentiation in the developing mammalian brain. Recent studies using transgenic mouse models have demonstrated that SFKs that are highly expressed in the adult brain regulate neuronal plasticity and behavior through tyrosine phosphorylation of key substrates such as neurotransmitter receptors. Here, we provide an overview of these recent studies, as well as discussing how modulation of the endocytosis of neurotransmitter receptors by SFKs contributes, in part, to this regulation. Deregulation of SFK-dependent tyrosine phosphorylation of such substrates might underlie certain brain disorders.

Introduction

The role of Src family kinases (SFKs) in the central nervous system (CNS) was originally thought to be limited to the regulation of the proliferation and differentiation of neuronal cells 1, 2. However, SFKs are also expressed in differentiated, postmitotic neurons, suggesting that these protein tyrosine kinases (PTKs) might also participate in the regulation of functions in the CNS beyond the developmental stage 3, 4, 5. Indeed, genetic ablation of SFKs such as Fyn or Lyn has been shown to result in behavioral abnormalities in adult mice 6, 7, suggesting that SFKs function in the regulation of neuronal plasticity and behavior. However, the molecular mechanisms of such regulation, in particular the identity of the relevant SFK substrates, remained largely unclear. Recent studies using genetically modified mouse models that either lack specific SFK substrates or have specific tyrosine phosphorylation sites mutated within substrates, have begun to shed light on these issues. Here, we provide an overview of recent progress in attempts to define the roles of SFKs in the regulation of neuronal function in the adult brain, with particular emphasis on the modulation of neurotransmitter receptors and behavior.

Section snippets

SFKs: general domain organization and activation mechanism

All SFKs share a conserved domain organization (Box 1). Autophosphorylation of a tyrosine residue (Y⁴¹⁶, according to the convention of numbering amino acid residues relative to chicken Src) in the activation loop of the kinase domain is thought to increase the PTK activity of SFKs. By contrast, phosphorylation by other kinases, such as C-terminal Src kinase (Csk) or Csk homologous kinase (Chk), of a tyrosine residue (Y⁵²⁷) near the COOH-terminus of SFKs suppresses the kinase activity.

Roles of SFKs in the regulation of synaptic transmission

Recent studies have indicated that SFKs regulate neuronal plasticity and behavior through tyrosine phosphorylation of neurotransmitter receptors. These receptors include ionotropic glutamate receptors of the NMDA and AMPA subclasses (NMDARs and AMPARs), which contribute to excitatory transmission, as well as GABA type A receptors (GABA_ARs), which mediate the majority of fast synaptic inhibition in the adult mammalian brain.

Importance of SFKs in the regulation of responsiveness to alcohol

Behavioral responses to drugs of abuse, such as cocaine, morphine and alcohol, are thought to be associated with functional modulation of neurotransmitter receptors and resultant changes in synaptic plasticity (reviewed in 56, 57). Regulation of neurotransmitter receptors by SFKs might thus contribute to drug-evoked plasticity changes and behavioral changes that occur in response to drugs of abuse.

Indeed, SFKs are implicated in the central action of alcohol. Fyn-deficient mice manifest an

Concluding remarks

SFK-mediated tyrosine phosphorylation of neurotransmitter receptors, including NMDARs, AMPARs and GABA_ARs, as well as modulatory signaling proteins, such as SIRPα has been implicated in the regulation of various brain functions (Figure 4). Phosphorylation-dependent modulation of receptor endocytosis might be a common mechanism underlying the regulation of neurotransmitter receptor function by SFKs. SFKs also mediate phosphorylation of other ion channels, such as large-conductance Ca²⁺-activated

Acknowledgments

The work in the authors’ laboratories was supported by a Grant-in-Aid for Scientific Research on Priority Areas Cancer, a Grant-in-Aid for Scientific Research (B), a Grant-in-Aid for Scientific Research (C), and a Global Center of Excellence Program grant from the Ministry of Education, Culture, Sports, Science and Technology of Japan.

References (94)

H. Umemori
Specific expressions of Fyn and Lyn, lymphocyte antigen receptor-associated tyrosine kinases, in the central nervous system
Brain Res. Mol. Brain Res.
(1992)
M. Sudol
Expression of proto-oncogenes in neural tissues
Brain Res.
(1988)
H. Umemori
Impairment of N-methyl-D-aspartate receptor-controlled motor activity in LYN-deficient mice
Neuroscience
(2003)
G.L. Collingridge
A nomenclature for ligand-gated ion channels
Neuropharmacology
(2009)
P. Paoletti et al.
NMDA receptor subunits: function and pharmacology
Curr. Opin. Pharmacol.
(2007)
J.Z. Tsien
The essential role of hippocampal CA1 NMDA receptor-dependent synaptic plasticity in spatial memory
Cell
(1996)
B.S. Chen et al.
Regulation of NMDA receptors by phosphorylation
Neuropharmacology
(2007)
T. Nakazawa
Characterization of Fyn-mediated tyrosine phosphorylation sites on GluRɛ2 (NR2B) subunit of the N-methyl-D-aspartate receptor
J. Biol. Chem.
(2001)
J.H. Hanke
Discovery of a novel, potent, and Src family-selective tyrosine kinase inhibitor. Study of Lck- and FynT-dependent T cell activation
J. Biol. Chem.
(1996)
K. Prybylowski
The synaptic localization of NR2B-containing NMDA receptors is controlled by interactions with PDZ proteins and AP-2
Neuron
(2005)

G. Lavezzari

Differential binding of the AP-2 adaptor complex and PSD-95 to the C-terminus of the NMDA receptor subunit NR2B regulates surface expression

Neuropharmacology

(2003)

M.A. Merrill

Activity-driven postsynaptic translocation of CaMKII

Trends Pharmacol. Sci.

(2005)

G. Fisone

Signaling in the basal ganglia: postsynaptic and presynaptic mechanisms

Physiol. Behav.

(2007)

T. Matozaki

Functions and molecular mechanisms of the CD47-SIRPα signalling pathway

Trends Cell Biol.

(2009)

C.M. Gladding

Tyrosine dephosphorylation regulates AMPAR internalisation in mGluR-LTD

Mol. Cell. Neurosci.

(2009)

R. Scholz

AMPA receptor signaling through BRAG2 and Arf6 critical for long-term synaptic depression

Neuron

(2010)

D.S. Bredt et al.

AMPA receptor trafficking at excitatory synapses

Neuron

(2003)

C.F. Valenzuela

Tyrosine kinase phosphorylation of GABA_A receptors

Brain Res. Mol. Brain Res.

(1995)

N.J. Brandon

Constitutive tyrosine phosphorylation of the GABA_A receptor γ2 subunit in rat brain

Neuropharmacology

(2001)

R. Jurd

Fyn kinase contributes to tyrosine phosphorylation of the GABA_A receptor γ2 subunit

Mol. Cell. Neurosci.

(2010)

G. Stupien

Involvement of the hippocampal CA3-region in acquisition and in memory consolidation of spatial but not in object information in mice

Neurobiol. Learn. Mem.

(2003)

M.R. Hunsaker

Behavioral characterization of a transection of dorsal CA3 subcortical efferents: comparison with scopolamine and physostigmine infusions into dorsal CA3

Neurobiol. Learn. Mem.

(2007)

C. Luscher et al.

Drug-evoked synaptic plasticity in addiction: from molecular changes to circuit remodeling

Neuron

(2011)

S.L. Boehm

Over-expression of the fyn-kinase gene reduces hypnotic sensitivity to ethanol in mice

Neurosci. Lett.

(2004)

O. Stork

Resistance to alcohol withdrawal-induced behaviour in Fyn transgenic mice and its reversal by ifenprodil

Brain Res. Mol. Brain Res.

(2002)

G. Schumann

Analysis of genetic variations of protein tyrosine kinase fyn and their association with alcohol dependence in two independent cohorts

Biol. Psychiatry

(2003)

I.J. Pastor

Genetic association between -93A/G polymorphism in the Fyn kinase gene and alcohol dependence in Spanish men

Eur. Psychiatry

(2009)

S.P. Braithwaite

Synaptic plasticity: one STEP at a time

Trends Neurosci.

(2006)

K.A. Pelkey

Tyrosine phosphatase STEP is a tonic brake on induction of long-term potentiation

Neuron

(2002)

T.H. Nguyen

Striatal enriched phosphatase 61 dephosphorylates Fyn at phosphotyrosine 420

J. Biol. Chem.

(2002)

M.R. Skelton

Protein tyrosine phosphatase α (PTPα) knockout mice show deficits in Morris water maze learning, decreased locomotor activity, and decreases in anxiety

Brain Res.

(2003)

M. Stein-Gerlach

SHP-2, SH2-containing protein tyrosine phosphatase-2

Int. J. Biochem. Cell Biol.

(1998)

T. Suzuki

Localization and subcellular distribution of SH-PTP2, a protein-tyrosine phosphatase with Src homology-2 domains, in rat brain

Biochem. Biophys. Res. Commun.

(1995)

S.Q. Zhang

Shp2 regulates SRC family kinase activity and Ras/Erk activation by controlling Csk recruitment

Mol. Cell

(2004)

B.G. Neel

The ‘Shp’ing news: SH2 domain-containing tyrosine phosphatases in cell signaling

Trends Biochem. Sci.

(2003)

P.F. Maness

Localization of the normal cellular src protein to the growth cone of differentiating neurons in brain and retina

Adv. Exp. Med. Biol.

(1990)

C.A. Ingraham

c-src and other proto-oncogenes implicated in neuronal differentiation

Mol. Chem. Neuropathol.

(1989)

C.A. Ross

Brain-specific src oncogene mRNA mapped in rat brain by in situ hybridization

Proc. Natl. Acad. Sci. U.S.A.

(1988)

S.G. Grant

Impaired long-term potentiation, spatial learning, and hippocampal development in fyn mutant mice

Science

(1992)

S.J. Parsons et al.

Src family kinases, key regulators of signal transduction

Oncogene

(2004)

M.W. Salter et al.

Src kinases: a hub for NMDA receptor regulation

Nat. Rev. Neurosci.

(2004)

Y.T. Wang et al.

Regulation of NMDA receptors by tyrosine kinases and phosphatases

Nature

(1994)

X.M. Yu

NMDA channel regulation by channel-associated protein tyrosine kinase Src

Science

(1997)

W. Zhao

Nonreceptor tyrosine protein kinase pp60c-src in spatial learning: synapse-specific changes in its gene expression, tyrosine phosphorylation, and protein-protein interactions

Proc. Natl. Acad. Sci. U.S.A.

(2000)

M. Yang et al.

Identification of mouse NMDA receptor subunit NR2A C-terminal tyrosine sites phosphorylated by coexpression with v-Src

J. Neurochem.

(2001)

T. Nakazawa

NR2B tyrosine phosphorylation modulates fear learning as well as amygdaloid synaptic plasticity

EMBO J.

(2006)

H.H. Cheung et al.

Tyrosine phosphorylation of the N-methyl-D-aspartate receptor by exogenous and postsynaptic density-associated Src-family kinases

J. Neurochem.

(2001)

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Disruption of the Src and NMDAR complex reduced neuropathic pain induced by peripheral nerve injury or inflammatory pain after intraplantar injection of complete Freund’s adjuvant or formalin (Liu et al., 2008). Notably, Src is activated by autophosphorylation at Tyr416 (a tyrosine residue of Src) in response to diverse stimuli (Ohnishi et al., 2011). Pannexin (Panx), a plasma membrane channel (Li et al., 2018), has three family members, Panx1, Panx2, and Panx3, which are permeable to molecules smaller than 1 kDa, such as ions and neurotransmitters, for example, the algogenic ATP molecule (MacVicar and Thompson, 2010; Li et al., 2018).
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Among nine known members of SFKs, five members are expressed in the brain. Fyn and Src, two key SFK members that have been most extensively studied and have drawn the most attention, are enriched at synaptic sites and actively modulate excitatory synaptic transmission and plasticity (Kalia et al., 2004; Ohnishi et al., 2011; Schenone et al., 2011; Mao et al., 2017). Of note, Src and especially Fyn are abundant in the striatum (Pascoli et al., 2011).
The Src family kinase (SFK) is a subfamily of non-receptor tyrosine kinases. The SFK member Fyn is enriched at synaptic sites in the limbic reward circuit and plays a pivotal role in the regulation of glutamate receptors. In this study, we investigated changes in phosphorylation and function of the two key SFK members (Fyn and Src) and SFK interactions with a metabotropic glutamate (mGlu) receptor in the limbic striatum of adult rats in response to chronic passive stress, i.e., prolonged social isolation which is a pre-validated animal paradigm modeling depression in adulthood. In rats that showed typical anhedonic/depression-like behavior after chronic social isolation, phosphorylation of SFKs at a conserved and activation-associated autophosphorylation site (Y416) was not altered in the two subdivisions of the striatum, the nucleus accumbens and caudate putamen. The total level of phosphorylation and kinase activity of individual Fyn and Src immunopurified from the striatum also remained stable after social isolation. Noticeably, Fyn and Src were found to interact with a G_αq-coupled mGlu5 receptor in striatal neurons. The interaction of Fyn with mGlu5 receptors was selectively elevated in socially isolated rats. Moreover, social isolation induced an increase in surface expression of striatal mGlu5 receptors, which was reduced by an SFK inhibitor. These results indicate that Fyn interacts with mGlu5 receptors in striatal neurons. Adulthood social isolation in rats enhances the Fyn-mGlu5 interaction, which appears to be critical for the upregulation of surface mGlu5 receptor expression in striatal neurons.

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Trends in Neurosciences

ReviewSrc family kinases: modulators of neurotransmitter receptor function and behavior

Introduction

Section snippets

SFKs: general domain organization and activation mechanism

Roles of SFKs in the regulation of synaptic transmission

Importance of SFKs in the regulation of responsiveness to alcohol

Concluding remarks

Acknowledgments

Brain Res. Mol. Brain Res.

Brain Res.

Neuroscience

Neuropharmacology

Curr. Opin. Pharmacol.

Cell

Neuropharmacology

J. Biol. Chem.

J. Biol. Chem.

Neuron

Neuropharmacology

Trends Pharmacol. Sci.

Physiol. Behav.

Trends Cell Biol.

Mol. Cell. Neurosci.

Neuron

Neuron

Brain Res. Mol. Brain Res.

Neuropharmacology

Mol. Cell. Neurosci.

Neurobiol. Learn. Mem.

Neurobiol. Learn. Mem.

Neuron

Neurosci. Lett.

Brain Res. Mol. Brain Res.

Biol. Psychiatry

Eur. Psychiatry

Trends Neurosci.

Neuron

J. Biol. Chem.

Brain Res.

Int. J. Biochem. Cell Biol.

Biochem. Biophys. Res. Commun.

Mol. Cell

Trends Biochem. Sci.

Localization of the normal cellular src protein to the growth cone of differentiating neurons in brain and retina

Adv. Exp. Med. Biol.

c-src and other proto-oncogenes implicated in neuronal differentiation

Mol. Chem. Neuropathol.

Brain-specific src oncogene mRNA mapped in rat brain by in situ hybridization

Proc. Natl. Acad. Sci. U.S.A.

Impaired long-term potentiation, spatial learning, and hippocampal development in fyn mutant mice

Science

Src family kinases, key regulators of signal transduction

Oncogene

Src kinases: a hub for NMDA receptor regulation

Nat. Rev. Neurosci.

Regulation of NMDA receptors by tyrosine kinases and phosphatases

Nature

NMDA channel regulation by channel-associated protein tyrosine kinase Src

Science

Nonreceptor tyrosine protein kinase pp60c-src in spatial learning: synapse-specific changes in its gene expression, tyrosine phosphorylation, and protein-protein interactions

Proc. Natl. Acad. Sci. U.S.A.

Identification of mouse NMDA receptor subunit NR2A C-terminal tyrosine sites phosphorylated by coexpression with v-Src

J. Neurochem.

NR2B tyrosine phosphorylation modulates fear learning as well as amygdaloid synaptic plasticity

EMBO J.

Tyrosine phosphorylation of the N-methyl-D-aspartate receptor by exogenous and postsynaptic density-associated Src-family kinases

J. Neurochem.

Review
Src family kinases: modulators of neurotransmitter receptor function and behavior