INVESTIGADORES
ARREGUI Carlos Oscar
artículos
Título:
The Juxtamembrane Domain of Cadherin Regulates Integrin- Mediated Adhesion and Neurite Outgrowth
Autor/es:
LILIEN, J; CARLOS OSCAR ARREGUI; LI, HD; BALSAMO, J
Revista:
JOURNAL OF NEUROSCIENCE RESEARCH
Editorial:
Wiley Interscience
Referencias:
Año: 1999 vol. 58 p. 727 - 734
ISSN:
0360-4012
Resumen:
Axons are guided along their trajectories during
development by many different systems of adhesion,
attraction, and repulsion. Thus, many distinct, and
potentially competing, receptor systems respond to
environmental cues, and the information must be
coordinated inside the growth cone to ensure that
extension follows the appropriate path. In this brief
review we bring together two studies, each of which
has defined different aspects of a pathway through
which N-cadherin regulates b1-integrin function allowing
for coordinated responses to environmental cues
during neurite extension. First we review progress in
defining the binding to cells and the subsequent effects
on adhesion and neurite outgrowth of the chondroitin
sulfate proteoglycan, neurocan. Neurocan binds to a
cell surface glycosyltransferase associated with Ncadherin
(but not integrin), initiating a signal which
results in loss of cadherin and integrin-function
suggesting that these two adhesion receptor systems engage
in cross-talk, allowing coordinate regulation. Second,
we review the use of Trojan peptides, peptides which
mimic specific sequences in the cytoplasmic domain of
N-cadherin attached to a cell permeation sequence, to
reveal proteinprotein interactions critical to cadherin
integrin cross-talk. One peptide mimicking a 20 amino
acid sequence in the juxtamembrane region of N-cadherin
has the same effect as neurocan, blocking both cadherinand
integrin-mediated adhesion and neurite outgrowth.
Both neurocan and the peptide cause the release of the
non-receptor tyrosine kinase Fer from the cadherin complex
and its binding to the integrin complex. These data
define an epigenetic pathway through which environmental
cues are capable of coordinately regulating the activity
of two developmentally important adhesion systems.