Figure 4.

Models of LRP4 involvement in central synapse development. LRP4 is required for synapse development in both invertebrate and vertebrate central nervous systems. In Drosophila (A), which lack both Agrin and MuSK homologues, LRP4 functions presynaptically in the olfactory system to instruct active zone formation. The ligand of LRP4 (and its exact source) remain unknown in this model. Two potential sources, a postsynaptic partner or glia, are indicated in this diagram. To instruct presynaptic changes, LRP4 functions through the downstream kinase, SRPK79D. In mouse cortical and hippocampal neurons (B), LRP4 functions in a similar manner to regulate synaptic density. It is unknown whether LRP4 functions primarily at the pre- or postsynapse; for the purposes of this model, it is shown as postsynaptic but could also function presynaptically. In these contexts, LRP4 induces presynaptic differentiation via an Agrin-dependent mechanism and regulates dendrite morphogenesis through a MuSK-dependent mechanism. In addition, LRP4 has important glial roles (in regulating growth and neurotransmission) and may be functioning in this role or in currently undiscovered functions.