title: Compensatory redistribution of neuroligins and N-cadherin following deletion of synaptic β1-integrin.
abstract: β1-containing integrins are required for persistent synaptic potentiation in hippocampus and regulate hippocampal-dependent learning. Based largely on indirect evidence, there is a prevailing assumption that β1-integrins are localized at synapses, where they contribute to synapse adhesion and signaling, but this has not been examined directly. Here we investigate the fine localization of β1-integrin in adult mouse hippocampus using high-resolution immunogold labeling, with a particular emphasis on synaptic labeling patterns. We find that β1-integrins localize to synapses in CA1 and are concentrated postsynaptically. At the postsynaptic membrane, β1-integrins are found more commonly clustered near active zone centers rather than at the peripheral edges. In mice harboring a conditional deletion of β1-integrins, labeling for N-cadherin and neuroligins increases. Western blots show increased levels of N-cadherin in total lysates and neuroligins increase selectively in synaptosomes. These data suggest there is a dynamic, compensatory adjustment of synaptic adhesion. Such adjustment is specific only for certain cell adhesion molecules (CAMs), because labeling for SynCAM is unchanged. Together, our findings demonstrate unequivocally that β1-integrin is an integral synaptic adhesion protein, and suggest that adhesive function at the synapse reflects a cooperative and dynamic network of multiple CAM families.
authors.affiliation: Department of Neuroscience, Friedman Brain Institute, Mount Sinai School of Medicine, New York, New York, USA.
authors.forename: Steven
authors.initials: S
authors.lastname: Mortillo
authors.forename: Alice
authors.initials: A
authors.lastname: Elste
authors.forename: Yongchao
authors.initials: Y
authors.lastname: Ge
authors.forename: Shekhar B
authors.initials: SB
authors.lastname: Patil
authors.forename: Kuangfu
authors.initials: K
authors.lastname: Hsiao
authors.forename: George W
authors.initials: GW
authors.lastname: Huntley
authors.forename: Ronald L
authors.initials: RL
authors.lastname: Davis
authors.forename: Deanna L
authors.initials: DL
authors.lastname: Benson
mesh_terms: D000818:Animals; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000235:genetics*; D006624:Hippocampus / Q000166:cytology* / Q000648:ultrastructure; D019012:Integrin beta1 / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016253:Microscopy, Immunoelectron / Q000379:methods; D013569:Synapses / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure
chemical_list: D015820:Cadherins; D015816:Cell Adhesion Molecules, Neuronal; D019012:Integrin beta1