Neuroligin-1 induces neurite outgrowth through interaction with neurexin-1ß and activation of fibroblast growth factor receptor-1.

ABSTRACT

Neurexin-1 (NRXN1) and neuroligin-1 (NLGN1) are synaptic cell adhesion molecules that connect pre- and postsynaptic neurons at synapses and mediate signaling across the synapse, which modulates synaptic activity and determines the properties of neuronal networks. Defects in the genes encoding NLGN1 have been linked to cognitive diseases such as autism. The roles of both NRXN1 and NLGN1 during synaptogenesis have been studied extensively, but little is known about the role of these molecules in neuritogenesis, which eventually results in neuronal circuitry formation. The present study investigated the neuritogenic effect of NLGN1 in cultures of hippocampal neurons. Our results show that NLGN1, both in soluble and membrane-bound forms, induces neurite outgrowth that depends on the interaction with NRXN1ß and on activation of fibroblast growth factor receptor-1. In addition, we demonstrate that a synthetic peptide, termed neurolide, which is modeled after a part of the binding interface of NLGN1 for NRXN1ß, can bind to NRXN1ß and mimic the biological properties of NLGN1 in vitro.