Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase expressed in neurons of the developing and adult brain in addition to non-neuronal cells. Activation of FAK is initiated by autophosphorylation of the kinase at tyrosine 397 (Y397). Active FAK transmits extracellular signals inside neurons to integrate cytoskeletal rearrangements and modulate synaptic transmission and plasticity.
View Article and Find Full Text PDFFive muscarinic acetylcholine (mACh) receptor subtypes are divided into two classes: the M1 class (M, M, and M) and the M2 class (M and M). The former is coupled to G proteins, while the latter is coupled to G proteins. Accumulating evidence indicates that mACh receptors play a significant role in the regulation of the Src family kinase (SFK), a subfamily of non-receptor tyrosine kinases.
View Article and Find Full Text PDFThe commonly used general anesthetic propofol can enhance the γ-aminobutyric acid-mediated inhibitory synaptic transmission and depress the glutamatergic excitatory synaptic transmission to achieve general anesthesia and other outcomes. In addition to the actions at postsynaptic sites, the modulation of presynaptic activity by propofol is thought to contribute to neurophysiological effects of the anesthetic, although potential targets of propofol within presynaptic nerve terminals are incompletely studied at present. In this study, we explored the possible linkage of propofol to synapsins, a family of neuron-specific phosphoproteins which are the most abundant proteins on presynaptic vesicles, in the adult mouse brain in vivo.
View Article and Find Full Text PDFMetabotropic glutamate (mGlu) receptors are G protein-coupled receptors. Among eight mGlu subtypes (mGlu1-8), mGlu8 has drawn increasing attention. This subtype is localized to the presynaptic active zone of neurotransmitter release and is among the mGlu subtypes with high affinity for glutamate.
View Article and Find Full Text PDFMetabotropic glutamate (mGlu) receptors are involved in the experience-dependent neuroplasticity in the mesolimbic reward circuit. A Gα-coupled mGlu2 subtype is distributed presynaptically in the striatum. These autoreceptors may have a significant influence over striatal neurons in their intracellular signaling pathways in response to a psychostimulant.
View Article and Find Full Text PDFGroup II metabotropic glutamate (mGlu) receptors (mGlu2/3) are Gαi/o-coupled receptors and are primarily located on presynaptic axonal terminals in the central nervous system. Like ionotropic glutamate receptors, group II mGlu receptors are subject to regulation by posttranslational phosphorylation. Pharmacological evidence suggests that several serine/threonine protein kinases possess the ability to regulate mGlu2/3 receptors.
View Article and Find Full Text PDFMajor depressive disorder is a common and serious mood illness. The molecular mechanisms underlying the pathogenesis and symptomatology of depression are poorly understood at present. Multiple neurotransmitter systems are believed to be implicated in depression.
View Article and Find Full Text PDFActivation of protein kinases after cocaine administration controls psychomotor behaviours by interacting with metabotropic receptors in the brain. This study identified how c-Jun N-terminal kinase (JNK) interacts with metabotropic glutamate receptor 5 (mGluR5) in vitro and in the caudate and putamen (CPu). The potential role of this interaction in the regulation of psychomotor behaviour was also evaluated after administration of cocaine.
View Article and Find Full Text PDFMajor depressive disorder is a chronic psychiatric disease with a high prevalence. Brain mechanisms for depression at cellular and molecular levels are far from clear. Increasing evidence from clinical and preclinical studies reveals critical roles of the non-receptor tyrosine kinase (nRTK) superfamily in the pathophysiology, symptomatology, and therapy of depression.
View Article and Find Full Text PDFGroup I metabotropic glutamate (mGlu) receptors (mGlu1/5 subtypes) are G protein-coupled receptors and are broadly expressed in the mammalian brain. These receptors play key roles in the modulation of normal glutamatergic transmission and synaptic plasticity, and abnormal mGlu1/5 signaling is linked to the pathogenesis and symptomatology of various mental and neurological disorders. Group I mGlu receptors are noticeably regulated via a mechanism involving dynamic protein-protein interactions.
View Article and Find Full Text PDFAdenosine A receptors are G-coupled receptors and are predominantly expressed in the striatum of mammalian brains. As a mostly postsynaptic receptor, A receptors are implicated in the regulation of a variety of intracellular signaling pathways in striatopallidal output neurons and are linked to the pathogenesis of various neuropsychiatric and neurological disorders. This study investigated the possible role of A receptors in the modulation of the Src family kinase (SFK) in the adult rat striatum.
View Article and Find Full Text PDFAdenosine A receptors are widely expressed in the mammalian brain. Through interacting with G -coupled A receptors, the neuromodulator adenosine modulates a variety of cellular and synaptic activities. To determine the linkage from A receptors to a key intracellular signaling pathway, we investigated the impact of blocking A receptors on a subfamily of nonreceptor tyrosine kinases, that is, the Src family kinase (SFK), in different rat brain regions in vivo.
View Article and Find Full Text PDFThe 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.
View Article and Find Full Text PDFObjective: The adenosine A receptor is a G protein-coupled receptor and inhibits upon activation cAMP formation and protein kinase A (PKA) activity. As a widely expressed receptor in the mammalian brain, A receptors are implicated in the modulation of a variety of neuronal and synaptic activities. In this study, we investigated the role of A receptors in the regulation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors in the adult rat brain in vivo.
View Article and Find Full Text PDFThe extracellular signal-regulated kinase (ERK) is enriched in the central nervous system, including the dopamine responsive regions such as the striatum and medial prefrontal cortex (mPFC). The kinase is sensitive to changing cellular and synaptic input and is implicated in the regulation of synaptic transmission and plasticity. In this study, the role of a G protein-coupled adenosine A receptor in the regulation of ERK1/2 was investigated in the rat brain in vivo.
View Article and Find Full Text PDFThe medial prefrontal cortex (mPFC) is implicated in the rewarding effect of psychostimulants, although molecular mechanisms underlying the rewarding properties of stimulants in this region are poorly understood. Group I metabotropic glutamate (mGlu) receptors (mGlu1/5 subtypes) are believed to be critical in this event. We thus in this study investigated changes in mGlu1/5 receptor expression and function in the rat mPFC in response to conditioned place preference (CPP) induced by amphetamine.
View Article and Find Full Text PDFThe metabotropic glutamate (mGlu) receptor 5 is a G protein-coupled receptor and is densely expressed in the mammalian brain. Like other glutamate receptors, mGlu5 receptors are tightly regulated by posttranslational modifications such as phosphorylation, although underlying mechanisms are incompletely investigated. In this study, we investigated the role of a prime kinase, extracellular signal-regulated kinase 1 (ERK1), in the phosphorylation and regulation of mGlu5 receptors in vitro and in striatal neurons.
View Article and Find Full Text PDFThe psychostimulant amphetamine (AMPH) has an impact on a variety of cellular activities in striatal neurons, although underlying signaling mechanisms are incompletely understood. The Src family kinase (SFK) is among key signaling molecules enriched in striatal neurons and is involved in the regulation of a set of discrete downstream targets. Given the likelihood that AMPH may regulate SFKs, we investigated and characterized the effect of AMPH on SFK phosphorylation and enzymatic activity in rat striatal neurons in vivo.
View Article and Find Full Text PDFMol Ther Nucleic Acids
September 2018
Doxorubicin is a widely used anthracycline-based anti-tumor agent for both solid and liquid tumors. Mounting evidence has demonstrated that microRNAs (miRNAs) are involved in chemoresistance and tumorigenesis. However, the roles of microRNA-501-5p (miR-501) in doxorubicin resistance and gastric cancer cell proliferation and invasion are still not fully understood.
View Article and Find Full Text PDFThe mitogen-activated protein kinase (MAPK), especially its extracellular signal-regulated kinase (ERK) subfamily, is a group of kinases enriched in the mammalian brain. While ERK is central to cell signaling and neural activities, the regulation of ERK by transmitters is poorly understood. In this study, the role of acetylcholine in the regulation of ERK was investigated in adult rat striatum in vivo.
View Article and Find Full Text PDFThe Src family kinase (SFK) is a subfamily of non-receptor tyrosine kinases. SFK members, Src and especially Fyn, are expressed in the striatum. These SFK members are involved in the regulation of neuronal and synaptic activities and are linked to the pathogenesis of a variety of neuropsychiatric and neurodegenerative disorders.
View Article and Find Full Text PDFThe acetylcholine muscarinic 4 (M4) receptor is a principal muscarinic receptor subtype present in the striatum. Notably, G-coupled M4 receptors and G/G-coupled dopamine D1 receptors are coexpressed in striatonigral projection neurons and are thought to interact with each other to regulate neuronal excitability, although underlying molecular mechanisms are poorly understood. In this study, we investigated the role of M4 receptors in the regulation of phosphorylation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors in the rat normal and dopamine-stimulated striatum in vivo.
View Article and Find Full Text PDFMajor depressive disorder is a common form of mental illness. Many brain regions are implicated in the pathophysiology and symptomatology of depression. Among key brain areas is the striatum that controls reward and mood and is involved in the development of core depression-like behavior in animal models of depression.
View Article and Find Full Text PDFTwo key transmitters in the medial prefrontal cortex (mPFC), dopamine and acetylcholine, are believed to interact with each other to modulate local glutamatergic transmission, although molecular mechanisms underlying their crosstalk are poorly understood. Here we investigated effects of pharmacological manipulations of dopamine and muscarinic receptors on phosphorylation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors in the adult rat mPFC in vivo. We found that an agonist selective for G-coupled dopamine D receptors, SKF81297, increased AMPA receptor GluA1 subunit phosphorylation at a protein kinase A-sensitive site (S845), while SKF81297 had no effect on GluA1 phosphorylation at S831.
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