Hai scaricato questo file 0 volte nelle ultime 24 ore, il limite è 5.
Il totale dei file scaricati è 0 nelle ultime 24 ore, il limite è 5.

E-cadherin endocytosis regulates the activity of Rap1: a traffic light GTPase at the crossroads between cadherin and integrin function Scarica

The coordinate modulation of cadherin and integrin
functions plays an essential role in fundamental
physiological and pathological processes, including
morphogenesis and cancer. However, the molecular
mechanisms underlying the functional crosstalk between
cadherins and integrins are still elusive.
Here, we demonstrate that the small GTPase Rap1, a
crucial regulator of the inside-out activation of integrins, is
a target for E-cadherin-mediated outside-in signaling. In
particular, we show that a strong activation of Rap1 occurs
upon adherens junction disassembly that is triggered by Ecadherin
internalization and trafficking along the
endocytic pathway. By contrast, Rap1 activity is not
influenced by integrin outside-in signaling. Furthermore,
we demonstrate that the E-cadherin endocytosis-dependent
activation of Rap1 is associated with and controlled by an
increased Src kinase activity, and is paralleled by the
colocalization of Rap1 and E-cadherin at the perinuclear
Rab11-positive recycling endosome compartment, and the
association of Rap1 with a subset of E-cadherin-catenin
complexes that does not contain p120ctn. Conversely, Rap1
activity is suppressed by the formation of E-cadherindependent
cell-cell junctions as well as by agents that
inhibit either Src activity or E-cadherin internalization and
intracellular trafficking. Finally, we demonstrate that the
E-cadherin endocytosis-dependent activation of Rap1 is
associated with and is required for the formation of
integrin-based focal adhesions.
Our findings provide the first evidence of an E-cadherinmodulated
endosomal signaling pathway involving Rap1,
and suggest that cadherins may have a novel modulatory
role in integrin adhesive functions by fine-tuning Rap1
Inviato da:
Administrator (admin)
Inviato il
27 Jun 2011
Dimensioni del file:
1,233.74 Kb
Autore del file:
Fiorella Balzac1, Maria Avolio1, Simona Degani1, Irina Kaverina2, Mauro Torti3, Lorenzo Silengo1, J.
Inviato il
27 Jun 2011
Voti totali:0
Commenta per primo! Accedi o registrati, per favore.