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First published online August 9, 2006
doi: 10.1242/10.1242/jcs.03094

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Competition and cooperation between tenascin-R, lecticans and contactin 1 regulate neurite growth and morphology

¹ Max-Delbrück-Center for Molecular Medicine, R.-Rössle-Str.10, 13092 Berlin-Buch, Germany
² Department of Experimental Pathology, Institute for Clinical Sciences, Lunds University, University Hospital, Lund, Sweden

^* Author for correspondence (e-mail: uzachar{at}mdc-berlin.de)

Accepted 8 June 2006

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.

Key words: Tenascin-R, Chondroitin sulfate proteoglycans, Contactin 1, Neuritic microprocesses, Growth cone