The juxtamembrane domain of cadherin regulates integrin-mediated adhesion and neurite outgrowth

Axons are guided along their trajectories during development by many differ ent systems of adhesion, attraction, and repulsion, Thus, many distinct, an d potentially competing, receptor systems respond to environmental cues, an d the information must be coordinated inside the growth cone to ensure that extension follows the appropriate path, In this brief review we bring toge ther two studies, each of which has defined different aspects of a pathway through which N-cadherin regulates beta 1-integrin function allowing for co ordinated responses to environmental cues during neurite extension. First w e review progress in defining the binding to cells and the subsequent effec ts on adhesion and neurite outgrowth of the chondroitin sulfate proteoglyca n, neurocan, Neurocan binds to a cell surface glycosyltransferase associate d with N-cadherin (but not integrin), initiating a signal which results in loss of cadherin and integrin-function-suggesting that these two adhesion r eceptor systems engage in cross-talk, allowing coordinate regulation, Secon d, we review the use of "Trojan" peptides, peptides which mimic specific se quences in the cytoplasmic domain of N-cadherin attached to a cell permeati on sequence, to reveal protein-protein interactions critical to cadherin-in tegrin cross-talk. One peptide mimicking a 20 amino acid sequence in the ju xtamembrane region of N-cadherin has the same effect as neurocan, blocking both cadherin- and integrin-mediated adhesion and neurite outgrowth. Both n eurocan and the peptide cause the release of the non-receptor tyrosine kina se Fer from the cadherin complex and its binding to the integrin complex. T hese data define an epigenetic pathway through which environmental cues are capable of coordinately regulating the activity of two developmentally imp ortant adhesion systems, J. Neurosci. Res. 58:727-734, 1999. (C) 1999 Wiley -Liss, Inc.