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A two-tiered mechanism for stabilization and immobilization of E-cadherin

A two-tiered mechanism for stabilization and immobilization of E-cadherin. Matthiue Cavey , Matteo Rauzi , Pierre-François Lenne & Thomas Lecuit. Presented by Shig 3/5/10. Background: E-cadherin. Cadherin – calcium dependent adhesion molecules that mediate cell-cell interactions.

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A two-tiered mechanism for stabilization and immobilization of E-cadherin

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  1. A two-tiered mechanism for stabilization and immobilization of E-cadherin MatthiueCavey, MatteoRauzi, Pierre-François Lenne & Thomas Lecuit Presented by Shig 3/5/10

  2. Background: E-cadherin Cadherin – calcium dependent adhesion molecules that mediate cell-cell interactions E-cadherin – epithelial cadherin SAJ – spot adherens junction Homo-E-cad – E-cad homodimer that localizes at SAJs Role in development: – spatio-temporal cadherin levels change Role in adult – ie: intestine and bloodstream barrier

  3. Homophilic E-cadherin clusters in stable microdomains Figure 1: FRAP of E-cad-GFP Bright SAJ Low-intensity region Bright region FRAP Also demonstrated with E-cad-EosFP Photoconvert -> no exchange w/neighbors E-cad-GFP fusion

  4. Two dynamically distinct actin populations Figure 2: Didn’t observe depolymerization of all F-actin with latrunculin-A (Lat-A) Actin patches underlie SAJ stability: SAJs dimmer in Lat-A treated embryos.

  5. α-Cat is not essential for homo-E-cad stability Knockdown α-Cat by RNAi No detectible α-Cat in SAJs E-cad-β-Cat spots still colocalize with F-actin Traditional View F-actin α-catenin β-catenin E-cad Figure 2: α-Cat not required to retain Lat-A resistant F-actin patches at SAJs

  6. A tensile actin network controls mobility of SAJs Figure 3 Reorganize actin network: increase mobility of SAJs. RNAi Lat-A: prevents actin polymerization Bitesize: organizes actin filaments at cell junctions through Moesin (F-actin binding protein)

  7. A tensile actin network controls mobility of SAJs Figure 3 Fortify actin network: decrease mobility of SAJs. DiaCA: Diaphanous – promotes unbranchedactin elongation myrWasp: promotes cortical actin branching Rok inhibitor: removes myosin-II motors within the cortical actin network

  8. α-Cat mediates tethering ofhomo-E-cad by cortical actin Figure 3: α-Cat RNAi increases SAJ mobility

  9. α-Cat mediates tethering ofhomo-E-cad by cortical actin Figure 4: Nano-joule ablation to sever actin network Uncaged fluorescein

  10. Model: two-tiered stabilization and immobilization of E-cadherin Stability: homo-E-cad at SAJs is stable independent of α-catenin linker between E-Cad-β-Cat and actin? E-Cad-β-Cat-F-actin structural units Mobility: α-catenin links E-cad to actin actin rearrangement delocalizes E-cad factors acting on actin effect SAJ mobility

  11. Future directions • Calcium necessary for E-cad rigidity and adhesion • calcium regulation during development • More linkers between SAJs and actin? • genetic screen • Role of microtubules and associated proteins • Better characterization of nano-scissors

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