A conserved retromer-independent function for RAB-6.2 in C. elegans epidermis integrity.

Rab proteins are conserved small GTPases that coordinate intracellular trafficking essential to cellular function and homeostasis. RAB-6.2 is a highly conserved C. elegans ortholog of human RAB6 proteins. RAB-6.2 is expressed in most tissues in C. elegans and is known to function in neurons and in the intestine to mediate retrograde trafficking. Here, we show that RAB-6.2 is necessary for cuticle integrity and impermeability in C. elegans RAB-6.2 functions in the epidermis to instruct skin integrity. Significantly, we show that expression of a mouse RAB6A cDNA can rescue defects in C. elegans epidermis caused by lack of RAB-6.2, suggesting functional conservation across phyla. We also show that the novel function of RAB-6.2 in C. elegans cuticle development is distinct from its previously described function in neurons. Exocyst mutants partially phenocopy rab-6.2-null animals, and rab-6.2-null animals phenocopy mutants that have defective surface glycosylation. These results suggest that RAB-6.2 may mediate the trafficking of one or many secreted glycosylated cuticle proteins directly, or might act indirectly by trafficking glycosylation enzymes to their correct intracellular localization.

Neural regeneration in Caenorhabditis elegans.

Axon regeneration is a medically relevant process that can repair damaged neurons. This review describes current progress in understanding axon regeneration in the model organism Caenorhabditis elegans. Factors that regulate axon regeneration in C. elegans have broadly similar roles in vertebrate neurons. This means that using C. elegans as a tool to leverage discovery is a legitimate strategy for identifying conserved mechanisms of axon regeneration.

Acetylcholine signaling genes are required for cocaine-stimulated egg laying in Caenorhabditis elegans.

The toxicity and addictive liability associated with cocaine abuse are well-known. However, its mode of action is not completely understood, and effective pharmacotherapeutic interventions remain elusive. The cholinergic effects of cocaine on acetylcholine receptors, synthetic enzymes, and degradative enzymes have been the focus of relatively little empirical investigation. Due to its genetic tractability and anatomical simplicity, the egg laying circuit of the hermaphroditic nematode, Caenorhabditis elegans, is a powerful model system to precisely examine the genetic and molecular targets of cocaine in vivo. Here, we report a novel cocaine-induced behavioral phenotype in C. elegans, cocaine-stimulated egg laying. In addition, we present the results of an in vivo candidate suppression screen of synthetic enzymes, receptors, degradative enzymes, and downstream components of the intracellular signaling cascades of the main neurotransmitter systems that control C. elegans egg laying. Our results show that cocaine-stimulated egg laying is dependent on acetylcholine synthesis and synaptic release, functional nicotinic acetylcholine receptors, and the C. elegans acetylcholinesterases.

Notch signaling inhibits axon regeneration.

Many neurons have limited capacity to regenerate their axons after injury. Neurons in the mammalian central nervous system do not regenerate, and even neurons in the peripheral nervous system often fail to regenerate to their former targets. This failure is likely due in part to pathways that actively restrict regeneration; however, only a few factors that limit regeneration are known. Here, using single-neuron analysis of regeneration in vivo, we show that Notch/lin-12 signaling inhibits the regeneration of mature C. elegans neurons. Notch signaling suppresses regeneration by acting autonomously in the injured cell to prevent growth cone formation. The metalloprotease and gamma-secretase cleavage events that lead to Notch activation during development are also required for its activity in regeneration. Furthermore, blocking Notch activation immediately after injury improves regeneration. Our results define a postdevelopmental role for the Notch pathway as a repressor of axon regeneration in vivo.