Competition and cooperation between tenascin-R, lecticans and contactin 1 regulate neurite growth and morphology.
The extracellular matrix molecule tenascin-R (TN-R) and the proteoglycans of the lectican family show an overlapping distribution in the developing brain, have been implicated in similar cellular processes and form a complex network of interactions. Previously, we have demonstrated that TN-R induces microprocesses along neurites and enlarged growth cones of tectal cells by interacting with the cell adhesion molecule contactin 1. Here, we describe competition and cooperation between TN-R, lecticans and contactin 1, and their functional consequences for tectal cells. Aggrecan, brevican and neurocan inhibit the effects of TN-R on microprocess formation and growth cone size. This blocking effect is due to competition of lecticans with binding of TN-R to its neuronal receptor contactin 1, as shown by a sandwich-binding assay. Interaction of aggrecan with TN-R fibronectin type III domains 4-A is necessary for its inhibitory effect on both microprocess formation and TN-R binding to contactin 1. However, the chondroitin sulfate chains are not involved. Time-lapse video microscopy showed that aggrecan has no acute effect on motility and morphology of microprocesses and growth cones but induces long-term neurite retraction after pre-treatment with TN-R. In contrast to the competition described above, TN-R cooperates with brevican and neurocan to induce attachment of tectal cells and neurite outgrowth, probably by forming a bridge between the lectican substrate and contactin 1 as the neuronal receptor. Our findings suggest that a complex network of protein-protein interactions within the brain extracellular matrix, as shown here for TN-R and lecticans, is important for the fine-regulation of developmental processes such as microprocess formation along the neurite and neurite outgrowth.
Zacharias
Ute
U
Max-Delbrück-Center for Molecular Medicine, R.-Rössle-Str.10, 13092 Berlin-Buch, Germany. uzachar@mdc-berlin.de
Rauch
Uwe
U
D053674:Aggrecans; D000818:Animals; D001667:Binding, Competitive; D001921:Brain / Q000166:cytology / Q000378:metabolism*; D058581:Brevican; D019556:COS Cells; D015816:Cell Adhesion Molecules, Neuronal / Q000378:metabolism*; D002642:Chick Embryo; D002645:Chickens; D002522:Chlorocebus aethiops; D011508:Chondroitin Sulfate Proteoglycans / Q000378:metabolism*; D058966:Contactins; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D020439:Growth Cones / Q000378:metabolism; D037181:Lectins, C-Type / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D016501:Neurites / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D019063:Tenascin / Q000378:metabolism*
D053674:Aggrecans; D058581:Brevican; D015816:Cell Adhesion Molecules, Neuronal; D011508:Chondroitin Sulfate Proteoglycans; D058966:Contactins; D016326:Extracellular Matrix Proteins; D037181:Lectins, C-Type; D009419:Nerve Tissue Proteins; D019063:Tenascin; C074638:tenascin R