To communicate with one another, neurons use chemicals that range from classical neurotransmitters, such as serotonin, to neuropeptides like beta-endorphin. Neurons use the protein-like neuropeptides to initiate and modulate complex behaviors.

Before being sent to other cells, neuropeptides must travel from the cell body of a neuron out to its axons. In the cell body, neuropeptide precursor proteins and their processing enzymes join together to form dense core vesicles (DCVs). These membrane-enclosed sacs then travel to the axons. Along the way, DCVs discard unneeded components and develop into dense packages of neuropeptides and other factors involved in synaptic signaling. Recent research in glowing worms helps explain how the maturation of DCVs is regulated.

Properly functioning DCVs are essential for neuronal signaling. Caenorhabditis elegans that are unable to secrete DCVs are severely paralyzed. To better understand the process of DCV transport and secretion, researchers led by Kenneth Miller (Oklahoma Medical Research Foundation, Oklahoma City) performed a genetic screen for DCV regulators. They found that the protein UNC-108 regulates DVCs (J. Cell Biol. 186, 881–895; 2009). Specifically, some unc-108 mutations suppressed movement in hyperactive mutant worms. UNC-108 is homologous to the human Rab2 protein, which is involved in trafficking intracellular membranes.

Miller's group then studied how these unc-108 mutations affected DCV function. Stefan Eimer of the European Neuroscience Institute Göttingen (Germany) and colleagues also analyzed DCV movement in unc-108 mutants (J. Cell Biol. 186, 897–914; 2009). Both research groups found that the unc-108 mutants had defects in DCV signaling. Surprisingly, however, these mutant worms had unimpaired processing and secretion of neuropeptides.

To further investigate the unc-108 mutants, the research groups labeled neuropeptides in the DCVs with a fluorescent protein. They saw that mutant worms had decreased fluorescence in their axons, meaning the DCVs had discarded the fluorescent proteins before reaching the axons. Since the processing and secretion of neuropeptides had remained unchanged in the unc-108 mutants, the researchers concluded that the mutant UNC-108 protein must have caused the DCVs to lose some other cargo that is essential to proper DCV functioning.

The research teams hope to determine which essential components of the DCVs become discarded in unc-108 mutants. They also plan to explore potential mechanisms for how UNC-108 prevents the loss of this cargo in normally functioning worms, with the goal of learning more about the role of Rab2 in human neuron signaling.