Adherens Junction Turnover: Regulating Adhesion Through Cadherin Endocytosis, Degradation, and Recycling
Adherens junctions are important mediators of intercellular adhesion, but they are not static structures. They are regularly formed, broken, and rearranged in a variety of situations, requiring changes in the amount of cadherins, the main adhesion molecule in adherens junctions, present at the cell surface. Thus, endocytosis, degradation, and recycling of cadherins are crucial for dynamic regulation of adherens junctions and control of intercellular adhesion. In this chapter, we review the involvement of cadherin endocytosis in development and disease. We discuss the various endocytic pathways available to cadherins, the adaptors involved, and the sorting of internalized cadherin for recycling or lysosomal degradation. In addition, we review the regulatory pathways controlling cadherin endocytosis and degradation, including regulation of cadherin endocytosis by catenins, cadherin ubiquitination, and growth factor receptor signaling pathways. Lastly, we discuss the proteolytic cleavage of cadherins at the plasma membrane.
KeywordsAdherens Junction Endocytic Pathway P120 Binding Growth Factor Signaling Pathway Classical Cadherins
We would like to thank Victor Faundez as well as members of the Kowalczyk lab for insightful and engaging conversations during the preparation of this manuscript. We would also like to acknowledge funding from the National Institutes of Health (R01AR050501 and R01AR048266 to APK). BAN was supported by a fellowship from the American Heart Association (11PRE7590097).
- Behrens J, Vakaet L, Friis R, Winterhager E, Van Roy F, Mareel MM, Birchmeier W (1993) Loss of epithelial differentiation and gain of invasiveness correlates with tyrosine phosphorylation of the E-cadherin/beta-catenin complex in cells transformed with a temperature-sensitive v-SRC gene. J Cell Biol 120:757–766PubMedCrossRefGoogle Scholar
- Brouxhon S, Kyrkanides S, O’Banion MK, Johnson R, Pearce DA, Centola GM, Miller JN, McGrath KH, Erdle B, Scott G, Schneider S, VanBuskirk J, Pentland AP (2007) Sequential down-regulation of E-cadherin with squamous cell carcinoma progression: loss of E-cadherin via a prostaglandin E2-EP2 dependent posttranslational mechanism. Cancer Res 67:7654–7664PubMedCrossRefGoogle Scholar
- Lampugnani MG, Zanetti A, Corada M, Takahashi T, Balconi G, Breviario F, Orsenigo F, Cattelino A, Kemler R, Daniel TO, Dejana E (2003) Contact inhibition of VEGF-induced proliferation requires vascular endothelial cadherin, beta-catenin, and the phosphatase DEP-1/CD148. J Cell Biol 161:793–804CrossRefGoogle Scholar
- Maeda M, Johnson E, Mandal SH, Lawson KR, Keim SA, Svoboda RA, Caplan S, Wahl 3rd JK, Wheelock MJ, Johnson KR (2006) Expression of inappropriate cadherins by epithelial tumor cells promotes endocytosis and degradation of E-cadherin via competition for p120(ctn). Oncogene 25:4595–4604PubMedCrossRefGoogle Scholar
- Marambaud P, Shioi J, Serban G, Georgakopoulos A, Sarner S, Nagy V, Baki L, Wen P, Efthimiopoulos S, Shao Z, Wisniewski T, Robakis NK (2002) A presenilin-1/gamma-secretase cleavage releases the E-cadherin intracellular domain and regulates disassembly of adherens junctions. EMBO J 21:1948–1956PubMedCrossRefGoogle Scholar
- Roeth JF, Sawyer JK, Wilner DA, Peifer M (2009) Rab11 helps maintain apical crumbs and adherens junctions in the drosophila embryonic ectoderm. PLoS One 4(10):e7634. doi:10.1371/journal.pone.0007634Google Scholar
- Stairs DB, Bayne LJ, Rhoades B, Vega ME, Waldron TJ, Kalabis J, Klein-Szanto A, Lee JS, Katz JP, Diehl JA, Reynolds AB, Vonderheide RH, Rustgi AK (2011) Deletion of p120-catenin results in a tumor microenvironment with inflammation and cancer that establishes it as a tumor suppressor gene. Cancer Cell 19:470–483PubMedCrossRefGoogle Scholar
- Toyoshima M, Tanaka N, Aoki J, Tanaka Y, Murata K, Kyuuma M, Kobayashi H, Ishii N, Yaegashi N, Sugamura K (2007) Inhibition of tumor growth and metastasis by depletion of vesicular sorting protein Hrs: its regulatory role on E-cadherin and beta-catenin. Cancer Res 67:5162–5171PubMedCrossRefGoogle Scholar
- Yabuta T, Shinmura K, Tani M, Yamaguchi S, Yoshimura K, Katai H, Nakajima T, Mochiki E, Tsujinaka T, Takami M, Hirose K, Yamaguchi A, Takenoshita S, Yokota J (2002) E-cadherin gene variants in gastric cancer families whose probands are diagnosed with diffuse gastric cancer. Int J Cancer 101:434–441PubMedCrossRefGoogle Scholar