The lifecycle of secretory vesicles: Implications for dendritic transmitter release

Intercellular communication is essential to the integrative function of neurones and neuroendocrine cells. The vesicular storage and release of bioactive molecules (transmitter) represents the major pathway for intercellular signals to be transferred from the 'sender' to 'receiver' cell. This process, in which the transmitter-containing vesicles undergo fiision with the plasma membrane and thereby release their contents into the extracellular space, is an adaptation of the constitutive exocytosis that occurs in all eukaryotic cells, fulfilling the 'housekeeping' role of turnover of plasma membrane constituents (Figure 1). Regulated exocytosis occurs only in response to specific extracellular signals that induce the synthesis or release of intracellular second messengers (usually Ca²⁺); these in turn trigger the membrane-fusion machinery. As this volume testifies, considerable evidence supports the role of dendritic transmitter release in coordinating neuronal function. However, although evidence is accumulating for regulated exocytosis of 'classical' transmitters and peptides from dendrites, the molecular machinery and vesicle lifecycle in dendrites is poorly understood, in contrast to our understanding of synaptic or endocrine transmitter release. In an attempt to highlight major questions, challenges and opportunities for investigators analysing dendritic transmitter release, we first overview our understanding of the vesicle lifecycle and molecular events in regulated exocytosis from synaptic and endocrine model systems before exploring our current understanding of dendritic release. In Section 2 we provide a general overview of regulated exocytosis before comparing 'classical' synaptic transmitter release to that of peptide release m endocrine cells in Section 3. We highlight the key molecular events involved in the vesicle lifecycle (Section 4) and review the evidence for regulated exocytosis in dendrites in Section 5.