Immunology and Developmental Psychopathology

Granger, Gale A.; Granger, Steve W.

doi:10.1002/9780470939390.ch17

Cited by 5 publications

(6 citation statements)

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“…[10][11][12][13][14] Hence, unraveling the dynamic structure-function interplay during modifications at the CTD of AMPA receptors is pivotal to the field of targeted neuro-therapy, especially for treating several neurological and psychiatric disorders. [4][5][15][16][17][18][19][20][21][22][23][24][25] Crystallography provides structural information about the extracellular domains of AMPA receptors, 8 but the structure of the intracellular CTD still remains unresolved, perhaps due to its flexible nature. 13,26 Electrophysiological measurements provide information on functional responses of the receptor channels in the activated state by measuring the ion channel conductance.…”

Section: Introductionmentioning

confidence: 99%

“…Functional studies show that Ca 2+ mediated phosphorylation of the intracellular CTD (at Ser818, Ser831, and Thr840) within the AMPA GluA1 subunit plays an important role during long-term potentiation (LTP) of the synapses 11,[16][17][18][34][35] and enhances channel conductance. 10,[27][28][29][36][37] Phosphorylation at Ser818 and Thr840 has been shown to influence synaptic plasticity.…”

Section: Introductionmentioning

confidence: 99%

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Phosphorylation Induces Conformational Rigidity at the C-Terminal Domain of AMPA Receptors

et al. 2018

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The intracellular C-terminal domain (CTD) of AMPA (α-amino-3-hydroxy-5-methyl-4isoxazolepropionic acid) receptor undergoes phosphorylation at specific locations during longterm potentiation (LTP). This modification enhances conductance through the AMPA receptor ion channel and thus potentially plays a crucial role in modulating receptor trafficking and signaling. However, because the CTD structure is largely unresolved, it is difficult to establish if phosphorylation induces conformational changes that might play a role in enhancing channel conductance. Herein, we utilize single molecule Fӧrster Resonance Energy Transfer (smFRET) spectroscopy to probe the conformational changes of a section of the AMPA receptor CTD, under the conditions of point-mutated phosphomimicry. Multiple analysis algorithms fail to identify stable conformational states within the smFRET distributions, consistent with a lack of welldefined secondary structure. Instead, our results show that phosphomimicry induces conformational rigidity to the CTD and such rigidity is electrostatically tunable.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Phosphorylation Induces Conformational Rigidity at the C-Terminal Domain of AMPA Receptors

et al. 2018

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“…The finding that salivary UA levels are not confounded by inflammatory activity in the oral cavity is important for salivary bioscience research focusing on salivary UA as a marker of cardiometabolic risk. Unlike many commonly investigated salivary analytes (e.g., cortisol), the serum-saliva association for most cytokines is negligible, and the vast majority of variation in salivary cytokine levels is produced locally in the oral cavity [48][49][50]. Given the unique immune environment of the oral cavity, it was important to test whether salivary UA levels are influenced by, or index, differences in oral inflammatory activity.…”

Section: Discussionmentioning

confidence: 99%

The Validity, Stability, and Utility of Measuring Uric Acid in Saliva

Riis

Bryce

Matin³

et al. 2018

Biomark. Med.

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“…19 As such, they are essential to development, growth, and maintenance of most body tissues and organ systems. 20 In the face of an immune threat, the immune system produces proinflammatory cytokines to destroy it. Proinflammatory cytokines also act directly on the brain, leading to "sickness behavior" characterized by loss of appetite, fatigue, social withdrawal, depressed mood, irritability, and poor cognitive functioning.…”

Section: Linking the Brain And Immune System Cytokinesmentioning

confidence: 99%

The Science of Early Life Toxic Stress for Pediatric Practice and Advocacy

Riley²,

et al. 2013

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Young children who experience toxic stress are at high risk for a number of health outcomes in adulthood, including cardiovascular disease, cancers, asthma, and depression. The American Academy of Pediatrics has recently called on pediatricians, informed by research from molecular biology, genomics, immunology, and neuroscience, to become leaders in science-based strategies to build strong foundations for children's life-long health. In this report, we provide an overview of the science of toxic stress. We summarize the development of the neuroendocrine-immune network, how its function is altered by early life adversity, and how these alterations then increase vulnerability to disease. The fact that early environments shape and calibrate the functioning of biological systems very early in life is both a cautionary tale about overlooking critical periods in development and reason for optimism about the promise of intervention. Even in the most extreme cases of adversity, well-timed changes to children's environments can improve outcomes. Pediatricians are in a unique position to contribute to the public discourse on health and social welfare by explaining how factors that seem distal to child health may be the key to some of the most intractable public health problems of our generation. We consider the challenges and opportunities for preventing toxic stress in the context of contemporary pediatric practice.

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Immunology and Developmental Psychopathology

Cited by 5 publications

References 154 publications

Phosphorylation Induces Conformational Rigidity at the C-Terminal Domain of AMPA Receptors

Phosphorylation Induces Conformational Rigidity at the C-Terminal Domain of AMPA Receptors

The Validity, Stability, and Utility of Measuring Uric Acid in Saliva

The Science of Early Life Toxic Stress for Pediatric Practice and Advocacy

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