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.