Neuroligin expressed in nonneuronal cells triggers presynaptic development in contacting axons.
Most neurons form synapses exclusively with other neurons, but little is known about the molecular mechanisms mediating synaptogenesis in the central nervous system. Using an in vitro system, we demonstrate that neuroligin-1 and -2, postsynaptically localized proteins, can trigger the de novo formation of presynaptic structure. Nonneuronal cells engineered to express neuroligins induce morphological and functional presynaptic differentiation in contacting axons. This activity can be inhibited by addition of a soluble version of beta-neurexin, a receptor for neuroligin. Furthermore, addition of soluble beta-neurexin to a coculture of defined pre- and postsynaptic CNS neurons inhibits synaptic vesicle clustering in axons contacting target neurons. Our results suggest that neuroligins are part of the machinery employed during the formation and remodeling of CNS synapses.
Scheiffele
P
P
Department of Molecular and Cell Biology, University of California, Berkeley 94720, USA. scheiffe@uclink4.berkeley.edu
Fan
J
J
Choih
J
J
Fetter
R
R
Serafini
T
T
D000818:Animals; D019556:COS Cells; D015816:Cell Adhesion Molecules, Neuronal; D002454:Cell Differentiation; D018920:Coculture Techniques; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D008565:Membrane Proteins / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000502:physiology*; D009474:Neurons / Q000502:physiology* / Q000648:ultrastructure; D013569:Synapses / Q000502:physiology* / Q000648:ultrastructure
D015816:Cell Adhesion Molecules, Neuronal; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C093438:neuroligin 1; C098003:neuroligin 2