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Regulation of CDH1 Function
Summary
- Organism
- Homo sapiens (human)
- Reactome
- R-HSA-9764561
- PubChem
- R-HSA-9764561
- Description
-
- To function in formation of adherens junctions, CDH1 (E-cadherin) has to associate with catenin proteins at the plasma membrane. Beta-catenin (CTNNB1) and gamma-catenin (JUP, also known as plakoglobin) compete for the same binding spot on CDH1 C-terminus. In addition, delta-catenin (CTNND1, also known as p120 or CAS) also binds the C-terminus of CDH1. Alpha-catenin (CTNNA1) associates with CDH1 indirectly, through CTNNB1 or JUP. For establishment of adherens junctions between neighboring cells, CDH1 has to form an antiparallel complex that consists of two CDH1:catenin complexes from two opposing cells, arranged in an antiparallel fashion. Formation of an antiparallel complex requires the presence of CTNND1 in the CDH1:catenin complex and the presence of extracellular calcium (Chitaev and Troyanovsky 1998). Two CDH1 molecules from the same cell join in a parallel fashion to form a lateral CDH1 complex through dimerization of the N-terminal extracellular domains of CDH1. Formation of the lateral complex does not require the presence of calcium or CTNND1 (Chitaev and Troyanovsky 1998). Binding of CTNNB1 or JUP is critical for CDH1 stability and cell surface localization. In the absence of CTNNB1 or JUP binding, CDH1 is targeted to lysosomes for degradation. Overexpression of CTNND1 can partially rescue CDH1 from degradation in the absence of CTNNB1/JUP binding (Troyanovsky et al. 2011).
Although CTNND1 does not recruit CTNNA1 to the CDH1:catenin complex, it may engage in intra-complex interactions with CTNNA1 (Troyanovsky et al. 2011).
- To function in formation of adherens junctions, CDH1 (E-cadherin) has to associate with catenin proteins at the plasma membrane. Beta-catenin (CTNNB1) and gamma-catenin (JUP, also known as plakoglobin) compete for the same binding spot on CDH1 C-terminus. In addition, delta-catenin (CTNND1, also known as p120 or CAS) also binds the C-terminus of CDH1. Alpha-catenin (CTNNA1) associates with CDH1 indirectly, through CTNNB1 or JUP. For establishment of adherens junctions between neighboring cells, CDH1 has to form an antiparallel complex that consists of two CDH1:catenin complexes from two opposing cells, arranged in an antiparallel fashion. Formation of an antiparallel complex requires the presence of CTNND1 in the CDH1:catenin complex and the presence of extracellular calcium (Chitaev and Troyanovsky 1998). Two CDH1 molecules from the same cell join in a parallel fashion to form a lateral CDH1 complex through dimerization of the N-terminal extracellular domains of CDH1. Formation of the lateral complex does not require the presence of calcium or CTNND1 (Chitaev and Troyanovsky 1998). Binding of CTNNB1 or JUP is critical for CDH1 stability and cell surface localization. In the absence of CTNNB1 or JUP binding, CDH1 is targeted to lysosomes for degradation. Overexpression of CTNND1 can partially rescue CDH1 from degradation in the absence of CTNNB1/JUP binding (Troyanovsky et al. 2011).
Click on a node on the pathway to see its details. Glycoproteins are marked with a glycoprotein icon in their name.
| UniProt ID | Protein Name | Gene Symbol | Pathway Viewer |
|---|---|---|---|
| O60716 | Catenin delta-1 |
|
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| P12830 | Cadherin-1 |
|
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| P14923 | Junction plakoglobin |
|
view |
| P18206 | Vinculin |
|
view |
| P35221 | Catenin alpha-1 |
|
view |
| P35222 | Catenin beta-1 |
|
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| P60709 | Actin, cytoplasmic 1 |
|
view |
| P62736 | Actin, aortic smooth muscle |
|
view |
| P63261 | Actin, cytoplasmic 2 |
|
view |
| P68032 | Actin, alpha cardiac muscle 1 |
|
view |
