CLEC-38, a transmembrane protein with C-type lectin-like domains, negatively regulates UNC-40-mediated axon outgrowth and promotes presynaptic development in Caenorhabditis elegans.
In the developing nervous system, axons respond to various guidance cues to find their targets. The effects guidance cues have on an axon may change as an axon undergoes morphological changes, such as branching, turning, and synapse formation. The means by which these changes are regulated are not well understood. In Caenorhabditis elegans, the UNC-40/DCC (deleted in colorectal cancer) receptor mediates responses to the UNC-6/netrin guidance cue. Here, we show that CLEC-38, a protein with predicted transmembrane and C-type lectin-like domains, regulates UNC-40-mediated axon outgrowth as well as the organization of presynaptic terminals. We observe that, in genetic backgrounds sensitized for axon guidance defects, loss of clec-38 function can suppress defects in an UNC-40-dependent manner. Within migrating axons, clec-38 acts cell autonomously. Furthermore, loss of clec-38 function alters UNC-40::GFP (green fluorescent protein) expression. We also observe that loss of clec-38 function disrupts presynaptic patterning in animals with normal axon guidance and that there are genetic interactions between clec-38 and rpm-1, which encodes a protein implicated in regulating presynaptic assembly and axon morphology. We suggest CLEC-38 plays a role in promoting synapse assembly and refining axon outgrowth activity.
Kulkarni
Gauri
G
Department of Pathology and Laboratory Medicine, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway, New Jersey 08854-5636, USA.
Li
Haichang
H
Wadsworth
William G
WG
D000818:Animals; D030801:Animals, Genetically Modified; D001369:Axons / Q000502:physiology*; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D015815:Cell Adhesion Molecules / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000502:physiology*; D015536:Down-Regulation / Q000502:physiology*; D037181:Lectins, C-Type / Q000235:genetics / Q000502:physiology*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000502:physiology*; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology*; D017434:Protein Structure, Tertiary / Q000502:physiology; D013569:Synapses / Q000235:genetics / Q000378:metabolism*
C528966:CLEC-38 protein, C elegans; D029742:Caenorhabditis elegans Proteins; D015815:Cell Adhesion Molecules; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; C102174:UNC-40 protein, C elegans