A novel function for neurexin and neuroligin family members in promoting neurite outgrowth

ABSTRACT Neurexins and neuroligins are heterophilic cell adhesion molecules which interact with the cytoskeleton and play a role in synaptogenesis. However, they are also expressed prior to synapse formation, suggestive of additional functions. Other neuronally expressed cell adhesion molecules play a role in promoting neurite outgrowth in addition to their adhesive functions. Here, we demonstrate a novel role for neuroligin 1 in promoting neurite outgrowth in N1E-115 neuroblastoma cells. Further, we identify both the acetylcholinesterase-like domain and PDZ motif as essential requirements for this process. We demonstrate that neuroligin 2 and neurexin 1β can produce the cytoskeletal rearrangements required for neurite outgrowth in N1E-115 cells. Finally, we show expression of nlgn1, nlgn2, nrxn1 and nrxn2 in the developing murine spinal cord. Insight into the outgrowth-promoting effects of the neurexin-neuroligin complex is especially pertinent as defects in neurexin and neuroligin family members have been linked to the autism spectrum of neurodevelopmental disorders.