Compartmentalization of signaling in neurons: evolution and deployment

The localization of signal transduction machinery at synapses is a fundamental organizational feature of the nervous system that allows for highly complex integration of information coding processes. Synaptic communication evolved as multicellular organisms became more complex, and as selection pressures were placed on such organisms such that those capable of responding rapidly and specifically to environmental demands survived. Two obvious advantages of synaptic transmission (as opposed to endocrine or paracrine signaling) are that it provides for rapid intercellular communication over great distances and that it provides a high level of spatial specificity. There are several structural and functional aspects of synapses that set them apart from other cellular compartments, with many of the specializations subserving roles in synaptic signal transduction (e.g., neurotransmitter release from the presynaptic terminal and postsynaptic receptor activation and second messenger production). However, studies of developing nervous systems have shown that many synaptic signaling mechanisms are operative prior to synaptogenesis and play important roles in regulating growth cone behaviors, synaptogenesis, and even programmed cell death. Indeed, the concept that "ontogeny recapitulates phylogeny" can be effectively applied to the evolution of the synapse. As the embryo rapidly grows, neurons must elaborate axons and dendrites, establish functional synaptic connections, and maintain and adjust those connections as the organism matures. The purpose of this introductory article is to set the stage for the following articles by briefly reviewing fundamental aspects of the molecular and cellular biology of synapses in an evolutionary context.