| First Author | Hunter DD | Year | 2019 |
| Journal | J Comp Neurol | Volume | 527 |
| Issue | 1 | Pages | 67-86 |
| PubMed ID | 29023785 | Mgi Jnum | J:269906 |
| Mgi Id | MGI:6273924 | Doi | 10.1002/cne.24338 |
| Citation | Hunter DD, et al. (2019) CNS synapses are stabilized trans-synaptically by laminins and laminin-interacting proteins. J Comp Neurol 527(1):67-86 |
| abstractText | 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 beta2 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 alpha3, 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 alpha3 and dystroglycan can be co-immunoprecipitated with the laminin beta2 chain, demonstrating that they may bind laminins. In the absence of the laminin beta2 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, beta-dystroglycan (beta-DG) expression is altered, co-localization of beta-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 beta-DG, pikachurin is no longer closely associated with mGluR6 or alpha-DG in the Lamb2-null. These data suggest that laminins act as links among pre- and post-synaptic laminin receptors and alpha-DG and pikachurin in the synaptic space to maintain proper trans-synaptic alignment. |
