Heterocellular interaction enhances recruitment of α and β-catenins and ZO-2 into functional gap-junction complexes and induces gap junction-dependant differentiation of mammary epithelial cells

• Published in: Experimental cell research 2008-11, Vol.314 (18), p.3275-3291
• Main Authors: Talhouk, Rabih S., Mroue, Rana, Mokalled, Mayssa, Abi-Mosleh, Lina, Nehme, Ralda, Ismail, Ayman, Khalil, Antoine, Zaatari, Mira, El-Sabban, Marwan E.
• Format: Article
• Language: English
• Subjects: alpha Catenin - metabolism; Animals; Basement Membrane - metabolism; beta Catenin - metabolism; Catenin; Cell Adhesion - physiology; Cell Communication - physiology; Cell Cycle Proteins - metabolism; Cell Differentiation - physiology; Cell Membrane Permeability - physiology; Connexin 30; Connexin 43 - metabolism; Connexins; Connexins - metabolism; Epithelial Cells - cytology; Epithelial Cells - physiology; Female; Gap Junction beta-1 Protein; Gap Junctions - physiology; Lactation; Mammary Glands, Animal - cytology; Membrane Proteins - metabolism; Mice; Zonula adherens; Zonula Occludens-2 Protein
• ISSN: 0014-4827; 1090-2422
• DOI: 10.1016/j.yexcr.2008.07.030

Gap junctions (GJ) are required for mammary epithelial differentiation. Using epithelial (SCp2) and myoepithelial-like (SCg6) mouse-derived mammary cells, the role of heterocellular interaction in assembly of GJ complexes and functional differentiation (β-casein expression) was evaluated. Heterocellular interaction is critical for β-casein expression, independent of exogenous basement membrane or cell anchoring substrata. Functional differentiation of SCp2, co-cultured with SCg6, is more sensitive to GJ inhibition relative to homocellular SCp2 cultures differentiated by exogenous basement membrane. Connexin (Cx)32 and Cx43 levels were not regulated across culture conditions; however, GJ functionality was enhanced under differentiation-permissive conditions. Immunoprecipitation studies demonstrated association of junctional complex components (α-catenin, β-catenin and ZO−2) with Cx32 and Cx43, in differentiation conditions, and additionally with Cx30 in heterocellular cultures. Although β-catenin did not shuttle between cadherin and GJ complexes, increased association between connexins and β-catenin in heterocellular cultures was observed. This was concomitant with reduced nuclear β-catenin, suggesting that differentiation in heterocellular cultures involves sequestration of β-catenin in GJ complexes.