What are some alternative mechanisms in the regulation of adherens junctions?
Alternative mechanisms also exist to regulate AJ formation and function. For example, the membrane trafficking system plays a significant role by facilitating the transport of E-cadherin–β-catenin complexes from the endoplasmic reticulum (ER) where they form. This system also enables complex sorting in the Trans-Golgi Network, delivers the cadherin-β-catenin complex to the plasma membrane and controls recycling of adhesion components upon adhesion disassembly and cadherin internalization. The influence of these processes on cell-cell adhesion regulation has recently been reviewed [1] and is illustrated in several recent studies.
One such example used an epithelial cell line expressing mutant reggies and prion protein – which contribute to the recruitment of E-cadherin, one study proposed that AJ function is influenced by the reggie dependent regulation of EGFR internalization, which in turn controls the macropinocytosis and recycling of E-cadherin [2]. In another example the small GTPase Rab35 was shown to regulate the recycling of internalized cadherin back to the plasma membrane. Inhibition of this protein also prevented PIP5KIy from accumulating at the adhesion site which impeded PI(4,5)P2 production [3]. PI(4,5)P2 is required for complex formation and stability [4].
In summary, regulation of cell-cell junctions is controlled in a highly complex manner, being influenced by numerous cellular processes and components. The primary modes of regulation appear to be those discussed; namely posttranslational modification of core components and scaffolding proteins, as well as regulation via actin cytoskeleton dynamics. Importantly other major cellular processes such as membrane trafficking also contribute to the regulation of cell-cell adhesions and may influence any one of the steps in their formation and function.
References
- Ivanov AI, and Naydenov NG. Dynamics and regulation of epithelial adherens junctions: recent discoveries and controversies. Int Rev Cell Mol Biol 2013; 303:27-99. [PMID: 23445808]
- Solis GP, Schrock Y, Hülsbusch N, Wiechers M, Plattner H, and Stuermer CAO. Reggies/flotillins regulate E-cadherin-mediated cell contact formation by affecting EGFR trafficking. Mol. Biol. Cell 2012; 23(10):1812-25. [PMID: 22438585]
- Charrasse S, Comunale F, De Rossi S, Echard A, and Gauthier-Rouvière C. Rab35 regulates cadherin-mediated adherens junction formation and myoblast fusion. Mol. Biol. Cell 2012; 24(3):234-45. [PMID: 23197472]
- Ling K, Bairstow SF, Carbonara C, Turbin DA, Huntsman DG, and Anderson RA. Type I gamma phosphatidylinositol phosphate kinase modulates adherens junction and E-cadherin trafficking via a direct interaction with mu 1B adaptin. J. Cell Biol. 2007; 176(3):343-53. [PMID: 17261850]
