GRK5 Regulates Social Behavior Via Suppression of mTORC1 Signaling in Medial Prefrontal Cortex. 2018

Bing Niu, and Peipei Liu, and Minjie Shen, and Cao Liu, and Li Wang, and Feifei Wang, and Lan Ma
State Key Laboratory of Medical Neurobiology, School of Basic Medical Sciences and Institutes of Brain Science, and the Collaborative Innovation Center for Brain Science, Fudan University, Shanghai 200032, China.

Impairments in social behaviors are features of a number of psychiatric diseases associated with subtle alterations in the medial prefrontal cortex (mPFC) circuitry. G protein-coupled receptor kinase (GRK) 5 is widely expressing in the cortex, however, its role in regulation of the mPFC activity and the development of social behaviors and psychiatric disorders is unclear. Here, we found that GRK5 dificiency in mice caused social behavior impairments. Further morphological, electrophysiological, and biochemical analyses showed abnormal postsynaptic ultrastructure, impaired excitatory synaptic transmission, the increased association of raptor with mTOR, and overactivated mTORC1-S6K signaling in the mPFC of Grk5-/- mice. Conditional knockdown of GRK5 in the mPFC caused impairments in social interaction and social novelty recognition behaviors; whereas selectively overexpressing GRK5 in the mPFC of Grk5-/- mice rescued the social novelty recognition phenotype. Inhibition of the overactivated mTORC1-S6K signaling pathway by rapamycin or mGluR5 antagonist ameliorated the deficiency of the excitatory synaptic transmission in the mPFC and the social recognition of Grk5-/- mice. These results indicate that GRK5 is critical for maintaining normal mTORC1 signaling and connectivity in mPFC, and normal social behavior.

UI MeSH Term Description Entries
D007166 Immunosuppressive Agents Agents that suppress immune function by one of several mechanisms of action. Classical cytotoxic immunosuppressants act by inhibiting DNA synthesis. Others may act through activation of T-CELLS or by inhibiting the activation of HELPER CELLS. While immunosuppression has been brought about in the past primarily to prevent rejection of transplanted organs, new applications involving mediation of the effects of INTERLEUKINS and other CYTOKINES are emerging. Immunosuppressant,Immunosuppressive Agent,Immunosuppressants,Agent, Immunosuppressive,Agents, Immunosuppressive
D008297 Male Males
D008810 Mice, Inbred C57BL One of the first INBRED MOUSE STRAINS to be sequenced. This strain is commonly used as genetic background for transgenic mouse models. Refractory to many tumors, this strain is also preferred model for studying role of genetic variations in development of diseases. Mice, C57BL,Mouse, C57BL,Mouse, Inbred C57BL,C57BL Mice,C57BL Mice, Inbred,C57BL Mouse,C57BL Mouse, Inbred,Inbred C57BL Mice,Inbred C57BL Mouse
D005260 Female Females
D000076222 Mechanistic Target of Rapamycin Complex 1 An evolutionarily conserved multiprotein complex that functions as a cellular energy sensor and regulator of protein synthesis for cell growth and proliferation. It consists of TOR SERINE-THREONINE KINASES; REGULATORY-ASSOCIATED PROTEIN OF MTOR (RAPTOR); MLST8 PROTEIN; and AKT1 substrate 1 protein. The activity of the complex is regulated by SIROLIMUS; INSULIN; GROWTH FACTORS; PHOSPHATIDIC ACIDS; some amino acids or amino acid derivatives, and OXIDATIVE STRESS. TOR Complex 1,TORC1,Target of Rapamycin Complex 1,mTORC1,mTORC1 Complex,Complex, mTORC1
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D012919 Social Behavior Any behavior caused by or affecting another individual or group usually of the same species. Sociality,Behavior, Social,Behaviors, Social,Social Behaviors
D015398 Signal Transduction The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. Cell Signaling,Receptor-Mediated Signal Transduction,Signal Pathways,Receptor Mediated Signal Transduction,Signal Transduction Pathways,Signal Transduction Systems,Pathway, Signal,Pathway, Signal Transduction,Pathways, Signal,Pathways, Signal Transduction,Receptor-Mediated Signal Transductions,Signal Pathway,Signal Transduction Pathway,Signal Transduction System,Signal Transduction, Receptor-Mediated,Signal Transductions,Signal Transductions, Receptor-Mediated,System, Signal Transduction,Systems, Signal Transduction,Transduction, Signal,Transductions, Signal
D017397 Prefrontal Cortex The rostral part of the frontal lobe, bounded by the inferior precentral fissure in humans, which receives projection fibers from the MEDIODORSAL NUCLEUS OF THE THALAMUS. The prefrontal cortex receives afferent fibers from numerous structures of the DIENCEPHALON; MESENCEPHALON; and LIMBIC SYSTEM as well as cortical afferents of visual, auditory, and somatic origin. Anterior Prefrontal Cortex,Brodmann Area 10,Brodmann Area 11,Brodmann Area 12,Brodmann Area 47,Brodmann's Area 10,Brodmann's Area 11,Brodmann's Area 12,Brodmann's Area 47,Pars Orbitalis,Frontal Sulcus,Gyrus Frontalis Inferior,Gyrus Frontalis Superior,Gyrus Orbitalis,Gyrus Rectus,Inferior Frontal Gyrus,Lateral Orbitofrontal Cortex,Marginal Gyrus,Medial Frontal Gyrus,Olfactory Sulci,Orbital Area,Orbital Cortex,Orbital Gyri,Orbitofrontal Cortex,Orbitofrontal Gyri,Orbitofrontal Gyrus,Orbitofrontal Region,Rectal Gyrus,Rectus Gyrus,Straight Gyrus,Subcallosal Area,Superior Frontal Convolution,Superior Frontal Gyrus,Ventral Medial Prefrontal Cortex,Ventromedial Prefrontal Cortex,Anterior Prefrontal Cortices,Area 10, Brodmann,Area 10, Brodmann's,Area 11, Brodmann,Area 11, Brodmann's,Area 12, Brodmann,Area 12, Brodmann's,Area 47, Brodmann,Area 47, Brodmann's,Area, Orbital,Area, Subcallosal,Brodmanns Area 10,Brodmanns Area 11,Brodmanns Area 12,Brodmanns Area 47,Convolution, Superior Frontal,Convolutions, Superior Frontal,Cortex, Anterior Prefrontal,Cortex, Lateral Orbitofrontal,Cortex, Orbital,Cortex, Orbitofrontal,Cortex, Prefrontal,Cortex, Ventromedial Prefrontal,Cortices, Ventromedial Prefrontal,Frontal Convolution, Superior,Frontal Gyrus, Inferior,Frontal Gyrus, Medial,Frontal Gyrus, Superior,Frontalis Superior, Gyrus,Gyrus, Inferior Frontal,Gyrus, Marginal,Gyrus, Medial Frontal,Gyrus, Orbital,Gyrus, Orbitofrontal,Gyrus, Rectal,Gyrus, Rectus,Gyrus, Straight,Gyrus, Superior Frontal,Inferior, Gyrus Frontalis,Lateral Orbitofrontal Cortices,Olfactory Sulcus,Orbital Areas,Orbital Cortices,Orbital Gyrus,Orbitalis, Pars,Orbitofrontal Cortex, Lateral,Orbitofrontal Cortices,Orbitofrontal Cortices, Lateral,Orbitofrontal Regions,Prefrontal Cortex, Anterior,Prefrontal Cortex, Ventromedial,Prefrontal Cortices, Anterior,Region, Orbitofrontal,Subcallosal Areas,Sulcus, Frontal,Superior Frontal Convolutions,Superior, Gyrus Frontalis,Ventromedial Prefrontal Cortices
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus

Related Publications

Bing Niu, and Peipei Liu, and Minjie Shen, and Cao Liu, and Li Wang, and Feifei Wang, and Lan Ma
August 2022, Biological psychiatry,
Bing Niu, and Peipei Liu, and Minjie Shen, and Cao Liu, and Li Wang, and Feifei Wang, and Lan Ma
March 2020, iScience,
Bing Niu, and Peipei Liu, and Minjie Shen, and Cao Liu, and Li Wang, and Feifei Wang, and Lan Ma
March 2023, Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics,
Bing Niu, and Peipei Liu, and Minjie Shen, and Cao Liu, and Li Wang, and Feifei Wang, and Lan Ma
September 2022, Cellular and molecular life sciences : CMLS,
Bing Niu, and Peipei Liu, and Minjie Shen, and Cao Liu, and Li Wang, and Feifei Wang, and Lan Ma
June 2016, The Journal of neuroscience : the official journal of the Society for Neuroscience,
Bing Niu, and Peipei Liu, and Minjie Shen, and Cao Liu, and Li Wang, and Feifei Wang, and Lan Ma
March 2017, Trends in cognitive sciences,
Bing Niu, and Peipei Liu, and Minjie Shen, and Cao Liu, and Li Wang, and Feifei Wang, and Lan Ma
January 2020, Yi chuan = Hereditas,
Bing Niu, and Peipei Liu, and Minjie Shen, and Cao Liu, and Li Wang, and Feifei Wang, and Lan Ma
January 2016, The Journal of neuroscience : the official journal of the Society for Neuroscience,
Bing Niu, and Peipei Liu, and Minjie Shen, and Cao Liu, and Li Wang, and Feifei Wang, and Lan Ma
April 2015, The Journal of neuroscience : the official journal of the Society for Neuroscience,
Bing Niu, and Peipei Liu, and Minjie Shen, and Cao Liu, and Li Wang, and Feifei Wang, and Lan Ma
April 2018, Biological psychiatry,
Copied contents to your clipboard!