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KEY CONCEPTS

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  • Signal transduction refers to the processes by which signals between cells carried by neurotransmitters, hormones, trophic factors, and cytokines are converted into biochemical signals within cells.

  • Most neurotransmitter receptors can be divided into two classes by their signal transduction mechanism—one class involving activation of an ion channel that is intrinsic to the receptor and the other involving activation of G proteins.

  • Signal transduction can alter neuronal function on vastly different time scales ranging from very rapid (millisecond) changes in membrane potential produced by ligand-gated channels to changes over seconds produced by intracellular second messengers and protein kinases.

  • Many critical drugs that act on the nervous system are agonists or antagonists at G protein–coupled receptors.

  • Although second messengers such as 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.

  • The brain contains numerous other types of protein serine–threonine kinases that also play important roles in the regulation of cell function.

  • Neurotrophins, such as nerve growth factor and brain-derived neurotrophic factor, interact with a family of receptors termed receptor tyrosine kinases (Trks).

  • Certain cytokines act on receptors that activate Janus kinases, which in turn activate a family of transcription factors called signal transducers and activators of transcription (STATs).

  • Protein phosphatases, also categorized into serine–threonine or tyrosine subfamilies, reverse the actions of protein kinases and serve critical functions in cell regulation.

  • Many intracellular signaling pathways ultimately 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 a core promoter and recruit RNA polymerase.

  • DNA-binding sites for regulatory proteins are called regulatory elements, and the proteins that bind them are called transcription factors.

  • Each gene has a unique pattern of cellular expression and response to physiologic signals based on the combinatorial interaction of regulatory elements found within its regulatory regions.

  • Eukaryotic cells increase the diversity of proteins that can be produced from a single gene by alternatively splicing the exons within the primary transcript.

  • Mature (spliced) messenger RNAs are transported from the nucleus into the cytoplasm, where they are translated to proteins on organelles called ribosomes.

  • During and after translation, proteins are processed by cleavage into smaller proteins and by a variety of covalent modifications such as glycosylation.

  • Numerous families of transcription factors, with diverse regulatory and functional properties, control gene expression in the CNS under normal and pathological conditions.

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INTRODUCTION

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Signal transduction refers to the processes by which intercellular signals such as neurotransmitters, neurotrophic factors, circulating hormones, and cytokines produce intracellular biochemical alterations that in turn modify neuronal functioning including the regulation of gene expression. Intercellular signals and their receptors, generally located in the neuronal plasma membrane, represent only a small amount of all information processing in the brain. An understanding of the complex biochemical mechanisms that operate inside ...

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