Heterocellular interaction enhances recruitment of alpha and beta-catenins and ZO-2 into functional gap-junction complexes and induces gap junction-dependant differentiation of mammary epithelial cells.
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 (beta-casein expression) was evaluated. Heterocellular interaction is critical for beta-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 (alpha-catenin, beta-catenin and ZO-2) with Cx32 and Cx43, in differentiation conditions, and additionally with Cx30 in heterocellular cultures. Although beta-catenin did not shuttle between cadherin and GJ complexes, increased association between connexins and beta-catenin in heterocellular cultures was observed. This was concomitant with reduced nuclear beta-catenin, suggesting that differentiation in heterocellular cultures involves sequestration of beta-catenin in GJ complexes.
Talhouk
Rabih S
RS
Department of Biology, Faculty of Arts and Sciences, American University of Beirut, Beirut, Lebanon. rtalhouk@aub.edu.lb
Mroue
Rana
R
Mokalled
Mayssa
M
Abi-Mosleh
Lina
L
Nehme
Ralda
R
Ismail
Ayman
A
Khalil
Antoine
A
Zaatari
Mira
M
El-Sabban
Marwan E
ME
D000818:Animals; D001485:Basement Membrane / Q000378:metabolism; D002448:Cell Adhesion / Q000502:physiology; D002450:Cell Communication / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology; D002463:Cell Membrane Permeability / Q000502:physiology; D000075302:Connexin 30; D018031:Connexin 43 / Q000378:metabolism; D017630:Connexins / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology / Q000502:physiology*; D005260:Female; D017629:Gap Junctions / Q000502:physiology*; D008321:Mammary Glands, Animal / Q000166:cytology; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D062827:Zonula Occludens-2 Protein; D051178:alpha Catenin / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism*; D000097002:Gap Junction beta-1 Protein
D018797:Cell Cycle Proteins; D000075302:Connexin 30; D018031:Connexin 43; D017630:Connexins; D008565:Membrane Proteins; D062827:Zonula Occludens-2 Protein; D051178:alpha Catenin; D051176:beta Catenin; D000097002:Gap Junction beta-1 Protein; C100629:Gjb6 protein, mouse; C569047:Tjp2 protein, mouse