Synaptic targeting of neuroligin is independent of neurexin and SAP90/PSD95 binding.
Synaptic cell adhesion and synaptogenesis are thought to involve the interaction of neuroligin, a postsynaptic transmembrane protein, with its presynaptic ligand neurexin. Neuroligin also interacts with SAP90/PSD95, a multidomain scaffolding protein thought to recruit proteins to postsynaptic sites. Using expression of GFP-tagged versions of neuroligin in cultured hippocampal neurons, we find that neuroligin is targeted to synapses via intracellular sequences distinct from its SAP90/PSD95 binding site. A neuroligin mutant lacking the intracellular domain fails to target to synapses. These data indicate that postsynaptic targeting of neuroligin does not rely on the scaffolding action of SAP90/PSD95 and is not induced by binding to presynaptic neurexin. Neuroligin is rather targeted to synapses via a postsynaptic mechanism, which may precede and be necessary for subsequent recruitment of neurexin and other neuroligin interactors such as SAP90/PSD95, suggesting a pivotal position for neuroligin in a putative hierarchy of interactions assembling or stabilizing synapses.
Dresbach
Thomas
T
Institute for Anatomy and Cell Biology, Ruprecht-Karls-University Heidelberg, D-69120 Heidelberg, Germany.
Neeb
Antje
A
Meyer
Guido
G
Gundelfinger
Eckart D
ED
Brose
Nils
N
D000818:Animals; D015816:Cell Adhesion Molecules, Neuronal; D002478:Cells, Cultured; D000076122:Disks Large Homolog 4 Protein; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D010936:Plant Extracts; D011485:Protein Binding / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D000074407:SAP90-PSD95 Associated Proteins; D013569:Synapses / Q000235:genetics / Q000378:metabolism*
D015816:Cell Adhesion Molecules, Neuronal; D000076122:Disks Large Homolog 4 Protein; C501449:Dlg4 protein, rat; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D010936:Plant Extracts; D000074407:SAP90-PSD95 Associated Proteins; C483503:neurexan; C093438:neuroligin 1; C033652:postsynaptic density proteins