Key Concepts Signal transduction = processes by which signals between cells carried by NTs, hormones, trophic factors, and cytokines are converted into biochemical signals within cells :Most NT receptors can be divided into 2 classes by their signal transduction mechanism: oActivation of ion channel intrinsic to the receptor o Activation of G proteins :Signal transduction can alter neuronal function on vastly different time scales ranging from: o very rapid (millisecond) changes in membrane potential produced by ligand-gated channels o_Changes over seconds produced by intracellular 2nd messengers and protein kinases :Critical drugs that act on the NS are agonists or antagonists at G-protein coupled receptors :2nd messengers like cyclic nucleotides and Ca2+ may directly gate ion channels, their major role in intracellular signaling systems is to regulate protein serine-threonine kinases that phosphorylate other proteins Brain contains numerous other types of protein serine-threonine kinases that also play important roles in regulation of cell fxn Neurotrophins, such as nerve growth factor and BDNF interact with a family of receptors termed receptor tyrosine kinases (Trks) Certain cytokines act on receptors that activate Janus kinases, which in
activators of transcription (STATs) Protein phosphatases, also categorized into serine-threonine or tyrosine subfamilies, reverse the axns of protein kinases and serve critical fxns in cell regulation Many intracellular signaling pathways regulate gene expression Transcription is stimulated when an activator protein displaces nucleosomes, the major component of chromatin, permitting a complex of proteins, called general transcription factors, to bind DNA at core promoter and recruit RNA pol DNA-binding sites for regulatory proteins are called regulatory elements, and the proteins that bind them are called transcription factors Eukaryotic cells increase the diversity of proteins that can be produced
transcript Mature (spliced) mRNAs are transported from nucleus cytoplasm where they are translated Proteins are translated and then often modified by covalent modifications like glycosylation I. OVERVIEW OF SIGNAL TRANSDUCTION PATHWAYS 4 general patterns of signal transduction in brain:
o #1 Binding of NT to a multimeric plasma membrane protein that contains ligand-gated channel Protein-protein interaxns Used by: AA NTs ACh @ nicotinic receptors Serotonin ATP Heat o#2 Binding of NT to plasma membrane receptor that couples with a guanine nucleotide-binding protein or G protein 7 transmembrane domain structure N-term to extracell space, C-term to cytoplasm Binding of ligand G protein regulation of certain ion channels Triggering of complex cascade of intracellular messengers Leads to intracellular 2nd messengers and protein phosphorylation Protein phosphorylation = major currency of intracellular signal transduction pathways Protein phosphorylation describes a process by which protein kinases add phosphate groups to specific target proteins, and protein phosphates (PPPs) remove these phosphate groups o#3 Protein tyrosine kinases: phosphorylate proteins on tyrosine residues Used by most types of neurotrophic factors and cytokines Sometimes neurotrophic factor and protein kinase reside in a single protein Activation of protein tyrosine kinase triggers cascades of further protein phosphorylation #4 Transduction by all known steroid hormones and certain other lipophilic extracellular signals that cross plasma membrane and activate receptors in the neuronal cytoplasm Cytoplasmic receptors tran