The extracellular matrix protein laminin (LN) is thought to play a role in guiding visual system axons to their targets. During development, LN is localized along most of the routes followed by extend processes (neurites) in response to it. As development proceeds, retinal neurons lose the play a role in initiating the process of target innervation. Loss of response to LN might also contribute to the inability of retinal axons to regenerate following later injury. Although the above view of LN in the visual system is supported by many studies, a recent observation suggests unexpected complexity in the regulation of LN's effects on retinal neurons: If LN is treated with polyclonal antibodies specific to one of its protein domains (known as P1), it strongly promotes neurite regeneration by late embryonic retinal neurons. This is surprising because LN not treated with antibodies has no detectable effect on the same neurons (also, the antibodies do not themselves promote neurite growth). Interestingly, the receptor on late embryonic retinal neurons use to interact with untreated LN. Thus, retinal neurons have a receptor for LN that they do not use unless LN is somehow altered. Preliminary evidence suggest that anti-P1 antibodies bring about this alteration not simply by exposing a previously hidden site on the LN molecule, but possibly by altering the interaction between two activities located in different LN domains. Interestingly, an isoform of LN, known as merosin, possesses neurite regeneration activity for late embryonic retinal activities of LN and its isoforms can be regulated in previously unsuspected ways. Experiments are proposed to study how that regulation occurs. The receptor that late embryonic rat retinal neurons use to recognize anti-P1 tested LN will be identified. Three possible mechanisms by which anti-P1 antibodies activate a new function in LN will be tested. Studies will be carried out to determine the site on LN that anti-Pa antibodies recognize when they uncover new neurite outgrowth activity. These studies will lead to a better understanding of how molecules that control axon growth, such as LN, work. They are especially relevant to the visual system, because they suggest that growth and regeneration- promoting signals previously thought to be unavailable to retinal neurons may actually be available. Exploiting this fact could lead to new approaches for stimulating regeneration following retinal or brain injury.
| Ivins, J K; Colognato, H; Kreidberg, J A et al. (1998) Neuronal receptors mediating responses to antibodyactivated laminin-1. J Neurosci 18:9703-15 |
