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

TY - JOUR

T1 - Neuroligin-1 induces neurite outgrowth through interaction with neurexin-1ß and activation of fibroblast growth factor receptor-1

AU - Gjørlund, Michelle D

AU - Nielsen, Janne

AU - Pankratova, Stanislava

AU - Li, Shizhong

AU - Korshunova, Irina

AU - Bock, Elisabeth

AU - Berezin, Vladimir

PY - 2012/10

Y1 - 2012/10

N2 - 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 NRXN1β 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 NRXN1β, can bind to NRXN1β and mimic the biological properties of NLGN1 in vitro.

AB - 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 NRXN1β 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 NRXN1β, can bind to NRXN1β and mimic the biological properties of NLGN1 in vitro.

KW - Animals

KW - Cell Adhesion Molecules

KW - Cell Adhesion Molecules, Neuronal

KW - Cell Line

KW - Cells, Cultured

KW - Hippocampus

KW - Humans

KW - Mice

KW - Nerve Tissue Proteins

KW - Neurites

KW - Neurons

KW - Rats

KW - Receptor, Fibroblast Growth Factor, Type 1

KW - Surface Plasmon Resonance

U2 - 10.1096/fj.11-202242

DO - 10.1096/fj.11-202242

M3 - Journal article

C2 - 22750515

SN - 0892-6638

VL - 26

SP - 4174

EP - 4186

JO - F A S E B Journal

JF - F A S E B Journal

IS - 10

ER -