CNS synapses are stabilized trans-synaptically by laminins and laminin-interacting proteins.

The retina expresses several laminins in the outer plexiform layer (OPL), where they may provide an extracellular scaffold for synapse stabilization. Mice with a targeted deletion of the laminin β2 gene (Lamb2) exhibit retinal disruptions: photoreceptor synapses in the OPL are disorganized and the retinal physiological response is attenuated. We hypothesize that laminins are required for proper trans-synaptic alignment. To test this, we compared the distribution, expression, association and modification of several pre- and post-synaptic elements in wild-type and Lamb2-null retinae. A potential laminin receptor, integrin α3, is at the presynaptic side of the wild-type OPL. Another potential laminin receptor, dystroglycan, is at the post-synaptic side of the wild-type OPL. Integrin α3 and dystroglycan can be co-immunoprecipitated with the laminin β2 chain, demonstrating that they may bind laminins. In the absence of the laminin β2 chain, the expression of many pre-synaptic components (bassoon, kinesin, among others) is relatively undisturbed although their spatial organization and anchoring to the membrane is disrupted. In contrast, in the Lamb2-null, β-dystroglycan (β-DG) expression is altered, co-localization of β-DG with dystrophin and the glutamate receptor mGluR6 is disrupted, and the post-synaptic bipolar cell components mGluR6 and GPR179 become dissociated, suggesting that laminins mediate scaffolding of post-synaptic components. In addition, although pikachurin remains associated with β-DG, pikachurin is no longer closely associated with mGluR6 or α-DG in the Lamb2-null. These data suggest that laminins act as links among pre- and post-synaptic laminin receptors and α-DG and pikachurin in the synaptic space to maintain proper trans-synaptic alignment. © 2017 Wiley Periodicals, Inc.

Citation

Dale D Hunter, Mary K Manglapus, Galina Bachay, Thomas Claudepierre, Michael W Dolan, Kelly-Ann Gesuelli, William J Brunken. CNS synapses are stabilized trans-synaptically by laminins and laminin-interacting proteins. The Journal of comparative neurology. 2019 Jan 01;527(1):67-86

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PMID: 29023785

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