RT Journal Article
SR Electronic
T1 Presynaptic LRP4 Promotes Synapse Number and Function of Excitatory CNS Neurons
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 115907
DO 10.1101/115907
A1 Timothy J. Mosca
A1 David J. Luginbuhl
A1 Irving E. Wang
A1 Liqun Luo
YR 2017
UL http://biorxiv.org/content/early/2017/03/10/115907.abstract
AB Precise coordination of synaptic connections ensures proper information flow within circuits. The activity of presynaptic organizing molecules signaling to downstream pathways is essential for such coordination, though such entities remain incompletely known. We show that LRP4, a conserved transmembrane protein known for its postsynaptic roles, functions presynaptically as an organizing molecule. In the Drosophila brain, LRP4 preferentially localizes to excitatory neuron terminals at or near active zones. Loss of presynaptic LRP4 reduces excitatory (not inhibitory) synapse number, impairs active zone architecture, and abolishes olfactory attraction - the latter of which can be suppressed by reducing presynaptic GABAB receptors. LRP4 overexpression increases synapse number in excitatory and inhibitory neurons, suggesting an instructive role and a common downstream synapse addition pathway. Mechanistically, LRP4 functions via the conserved kinase SRPK79D to ensure normal synapse number and behavior. This highlights a presynaptic function for LRP4, enabling deeper understanding of how synapse organization is coordinated.