Complex ITGAV:ITGB3:L1CAM map

Complex composition:

  1. ITGB3 map
  2. ITGAV map
  3. L1CAM map



 EMT  map  / EMT_REGULATORS  map
 EMT  map  / ECM  map

In the endoplasmic reticulum, integrin subunits find their binding partners and form heterodimers.
Monomeric integrins never reach the cell surface.
Integrin aVb3 is distinct in its capacity to recognize the sequence Arg-Gly-Asp (RGD) in many extra-cellular matrix (ECM) components.
aVb3 can also interact with the neural cell adhesion molecule L1CAM; a member of the immunoglobulin superfamily (IgSF). In other words, aVb3 undergoes heterophilic binding with L1CAM
M21 cells display some aVb3-dependent adhesion and spreading on immunopurified human L1. Ligation between this ligand and aVb3 was also observed to promote significant haptotactic cell migration.
Significant aVb3-dependent adhesion and spreading was evident on a L1 fragment containing Ig-like domains 4, 5, and 6.
Importantly, mutation of an RGD sequence present in the sixth Ig-like domain of L1 abrogated M21 cell adhesion.
Despite high levels of L1 expression the M21 melanoma cells did not display significant adhesion via a homophilic L1-L1 interaction.
These data suggest that M21 melanoma cells recognize and adhere to L1 through a mechanism that is primarily heterophilic and integrin dependent.
Finally, we present evidence that melanoma cells can shed and deposit L1 in occluding ECM.
aVb3 may recognize L1 in a cell-cell or cell-substrate interaction.
Tumor metastasis involves many stage-specific adhesive interactions. The expression of several cell adhesion molecules, notably the integrin aVb3 has been associated with the metastatic potential of tumor cells.
In the context of in vitro monolayer of human lung microvascular, L1CAM was shown to serve as a potential ligand for aVb3 during melanoma transendothelial migration.
Also, polyclonal antibodies against L1 partially inhibited the transendothelial migration of melanoma cells.
However, addition of both L1 and aVb3 antibodies did not show additive effects, suggesting that they are components of the same adhesion system.
Together, the data suggest that interactions between the integrin aVb3 on melanoma cells and L1 on endothelial cells play an important role in the transendothelial migration of melanoma cells.
Integrin aVb3 on melanoma cells, and not endothelial cells, is involved in the transmigration process.
Because L1 is expressed in both melanoma and endothelial cells, it is possible that L1-L1 homophilic interactions at the heterotypic contacts might play a role in the transmigration of melanoma cells.
The data thus indicate that transendothelial migration does not involve L1-L1 homophilic binding.
These results led us to speculate that L1 on endothelial cells, and not melanoma cells, has a role during transendothelial migration of melanoma cells
L1 also interacts heterophilically with laminin in the context of mouse small cerebellar neurons
Integrins (b1, a3, a6) could be shown to bind to laminin by a b1-dependent adhesion mechanism.
L1 was demonstrated to bind in a concentration-dependent and saturating manner to laminin.
Furthermore, antibodies to the Ig-like domains of L1 and b1 integrin inhibited partially cell adhesion to laminin.
Binding of L1CAM to aVb3 or aVb5 seemed to be pivotal for L1CAM-mediated cell migration leading to the activation of Erk1/2 and FAK signalling
In carcinoma cell lines, L1 overexpression augments cell motility, tumor growth in mice and induces expression of Erk-dependent genes
L1CAM-mediated Erk1/2 activate genes encoding for pro-migratory proteins such as cathepsin-B or b3-integrins were upregulated.
A mechanism in the glioma cells context was proposed: upregulated ADAM10 proteolyzes surface L1CAM and the resultant ectodomain of L1CAM increases human glioma cell migration and invasion by binding to integrin receptors, activating FAK, and increasing turnover of focal complexes.


Participates in complexes:
In compartment: Cytoplasm
  1. ITGAV:​ITGB3:​L1CAM@Cytoplasm map

Participates in reactions:
As Reactant or Product:

  1. L1CAM@Cytoplasm map + ITGAV:​ITGB3@Cytoplasm map map ITGAV:​ITGB3:​L1CAM@Cytoplasm map

  2. ITGAV:​ITGB3:​L1CAM@Cytoplasm map map Cell migration@Cytoplasm map

As Catalyser:

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