CLEC-38, A Transmembrane Protein with C-Type Lectin-Like Domains, Negatively Regulates UNC-40-Mediated Axon Outgrowth and Promotes Presynaptic Development inCaenorhabditis elegans

Abstract

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.

The Roles of Multiple UNC-40 (DCC) Receptor-Mediated Signals in Determining Neuronal Asymmetry Induced by the UNC-6 (Netrin) Ligand

“…For example, in contrast to the unc-40(ur304) phenotypes, the expression of a constitutively activated UNC-40 protein, MYRTUNC-40, causes enlarged and deformed cell bodies and additional axons and branches, as well as misguided axons (Gitai et al 2003). Previously, we showed that loss of clec-38 enhances UNC-40 activity and that, in clec-38 loss-offunction mutants that express the unc-40Tgfp transgene, the HSN develops severe morphological defects (see Figure 7 in Kulkarni et al 2008). Moreover, we observed that UNC-40 at the early L2 stage is ventrally asymmetrically localized in these mutants (Figure 3).…”

ChondrolectinMediates Growth Cone Interactions of Motor Axons with an Intermediate Target

“…To our knowledge, chodl is the first C-type lectin to be implicated in axon pathfinding in vertebrates. In C. elegans another C-type lectin, CLEC-38, has been shown to be involved in dorsal axon guidance (Kulkarni et al, 2008).…”

Genetic Associations of Brain Structural Networks in Schizophrenia: A Preliminary Study

“…Also, pathway analysis of genes illustrates how brain morphology and function may be influenced by processes including neuronal growth, migration, communication, and pruning. In this regard, axonal guidance signaling establishes normal connectivity between developing neurons and helps orient and promote axonal outgrowth (52,53). AKT2, PIK3CA , PIK3CB, and GNB3 were the relevant genes expressed in this signaling pathway.…”