Subject(s)
Biology , Amygdala/physiology , Cell Death , DNA Methylation/genetics , Food , Immunity, Innate/immunologySubject(s)
Anesthetics/pharmacology , Sleep/drug effects , Sleep/physiology , Anesthesia , Animals , Humans , Hypothalamus/cytology , Hypothalamus/drug effects , Hypothalamus/physiology , Isoflurane/pharmacology , Mice , Wakefulness/drug effects , Wakefulness/physiology , gamma-Aminobutyric Acid/metabolismSubject(s)
Cooperative Behavior , Group Processes , Social Justice , Age Factors , Animals , Child, Preschool , Food , Humans , Models, Psychological , Pan troglodytes/psychology , Play and Playthings , RewardSubject(s)
Protozoan Proteins/metabolism , Trypanosoma brucei brucei/growth & development , Trypanosoma brucei brucei/metabolism , Aconitic Acid/analogs & derivatives , Aconitic Acid/metabolism , Animals , Cell Differentiation , Citric Acid/metabolism , Gene Expression Regulation, Developmental , Humans , Insect Vectors/parasitology , Protozoan Proteins/genetics , Temperature , Trypanosoma brucei brucei/cytology , Trypanosoma brucei brucei/genetics , Trypanosomiasis, African/parasitology , Tsetse Flies/parasitologySubject(s)
Obesity/genetics , Obesity/metabolism , Oxo-Acid-Lyases/genetics , Oxo-Acid-Lyases/metabolism , Alpha-Ketoglutarate-Dependent Dioxygenase FTO , Animals , Energy Metabolism/genetics , Genetic Variation/genetics , Genotype , Humans , Mice , Mixed Function Oxygenases , Movement , Oxo-Acid-Lyases/deficiencySubject(s)
Glutamic Acid/metabolism , Receptors, G-Protein-Coupled/metabolism , Taste/physiology , Glutamic Acid/pharmacology , Guanosine Monophosphate/metabolism , Guanosine Monophosphate/pharmacology , Humans , Inosine Monophosphate/metabolism , Inosine Monophosphate/pharmacology , Taste/drug effects , Taste Buds/drug effects , Taste Buds/metabolismABSTRACT
Of many lipid transfer proteins identified, all have been implicated in essential cellular processes, but the activity of none has been demonstrated in intact cells. Among these, phosphatidylinositol transfer proteins (PITP) are of particular interest as they can bind to and transfer phosphatidylinositol (PtdIns)--the precursor of important signalling molecules, phosphoinositides--and because they have essential functions in neuronal development (PITPalpha) and cytokinesis (PITPbeta). Structural analysis indicates that, in the cytosol, PITPs are in a 'closed' conformation completely shielding the lipid within them. But during lipid exchange at the membrane, they must transiently 'open'. To study PITP dynamics in intact cells, we chemically targeted their C95 residue that, although non-essential for lipid transfer, is buried within the phospholipid-binding cavity, and so, its chemical modification prevents PtdIns binding because of steric hindrance. This treatment resulted in entrapment of open conformation PITPs at the membrane and inactivation of the cytosolic pool of PITPs within few minutes. PITP isoforms were differentially inactivated with the dynamics of PITPbeta faster than PITPalpha. We identify two tryptophan residues essential for membrane docking of PITPs.