Department of Clinical Laboratory, the Second Affiliated Hospital of Dalian Medical University, Dalian 116023, China.
Department of Orthopaedics Surgery, the First Affiliated Hospital of Dalian Medical University, Dalian 116011, China.
Acta Biochim Biophys Sin (Shanghai). 2022 Mar 25;54(3):400-408. doi: 10.3724/abbs.2022011.
Tetraspanin CD82 often participates in regulating the function of epidermal growth factor receptor (EGFR) and hepatocyte growth factor receptor (c-Met). Palmitoylation is a post-translational modification that contributes to tetraspanin web formation and affects tetraspanin-dependent cell signaling. However, the molecular mechanisms by which CD82 palmitoylation affects the localization and stability of EGFR and c-Met have not yet been elucidated. This study focuses on the expression and distribution of EGFR and c-Met in breast cancer as well as the related metabolic pathways and molecular mechanisms associated with different CD82 palmitoylation site mutations. The results show that CD82 with a palmitoylation mutation at Cys5+Cys74 can promote the internalization of EGFR. EGFR is internalized and strengthened by direct binding to CD82 with the tubulin assistance and located at the recycling endosome. After studying the recycling pathway marker proteins Rab11a and FIP2, we found that formation of the EGFR/CD82/Rab11a/FIP2 complex promotes the internalization and metabolism of EGFR through the recycling pathway and results in the re-expression of EGFR and CD82 on the cell membrane.
四跨膜蛋白 CD82 通常参与调节表皮生长因子受体 (EGFR) 和肝细胞生长因子受体 (c-Met) 的功能。棕榈酰化是一种翻译后修饰，有助于四跨膜蛋白形成网络，并影响四跨膜蛋白依赖的细胞信号转导。然而，CD82 棕榈酰化如何影响 EGFR 和 c-Met 的定位和稳定性的分子机制尚未阐明。本研究关注 EGFR 和 c-Met 在乳腺癌中的表达和分布，以及与不同 CD82 棕榈酰化位点突变相关的相关代谢途径和分子机制。结果表明，Cys5+Cys74 处棕榈酰化突变的 CD82 可促进 EGFR 的内化。在微管的协助下，CD82 与 EGFR 直接结合，将 EGFR 内化并加强，定位在再循环内体。在研究了再循环途径标记蛋白 Rab11a 和 FIP2 之后，我们发现 EGFR/CD82/Rab11a/FIP2 复合物的形成通过再循环途径促进 EGFR 的内化和代谢，导致 EGFR 和 CD82 在细胞膜上的重新表达。
