Increased internalization of p120-uncoupled E-cadherin and a requirement for a dileucine motif in the cytoplasmic domain for endocytosis of the protein
Increased internalization of p120-uncoupled E-cadherin and a requirement for a dileucine motif in the cytoplasmic domain for endocytosis of the protein
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DOI：
10.1074/jbc.m608351200
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发表时间：
2007-04-13
影响因子：
4.8
通讯作者：
Ozawa, Masayuki
中科院分区：
文献类型：
--
作者：
Miyashita, Yayoi;Ozawa, Masayuki
E-cadherin is a member of the cadherin family of Ca2+-dependent cell-cell adhesion molecules. E- cadherin associates with beta-catenin at the membrane-distal region of its cytosolic domain and with p120 at the membrane-proximal region of its cytoplasmic domain. It has been shown that a pool of cell surface E- cadherin is constitutively internalized and recycled back to the surface. Further, p120 knockdown by small interference RNA resulted in dose-dependent elimination of cell surface E- cadherin. Consistent with these observations, we found that selective uncoupling of p120 from E- cadherin by introduction of amino acid substitutions in the p120-binding site increased the level of E- cadherin endocytosis. The increased endocytosis was clathrin-dependent, because it was blocked by expression of a dominant-negative form of dynamin or by hypertonic shock. A dileucine motif in the juxtamembrane cytoplasmic domain is required for E-cadherin endocytosis, because substitution of these residues to alanine resulted in impaired internalization of the protein. The alanine substitutions in the p120- uncoupled construct reduced endocytosis of the protein, indicating that this motif was dominant to p120 binding in the control of E-cadherin endocytosis. Therefore, these results are consistent with the idea that p120 regulates E- cadherin endocytosis by masking the dileucine motif and preventing interactions with adaptor proteins required for internalization.
