Centre de Recherche, Centre Hospitalier de l'Université de Montréal (CRCHUM), Montréal, QC H2X 0A9, Canada; Département de Médecine, Université de Montréal, Montréal, QC H3T 1J4, Canada.
Centre de Recherche, Centre Hospitalier de l'Université de Montréal (CRCHUM), Montréal, QC H2X 0A9, Canada.
Cell Rep. 2018 Jul 17;24(3):670-684.e7. doi: 10.1016/j.celrep.2018.06.056.
COMMD5/HCaRG is involved in tissue repair, and its low expression is associated with tumorigenicity. Cell growth, migration, and differentiation are controlled by COMMD5. We previously reported that COMMD5 inhibited the growth of renal carcinoma cells by regulating expression or phosphorylation of ErbB members. Here, we demonstrate that COMMD5 is crucial for the stability of the cytoskeleton. Its silencing leads to a major re-organization of actin and microtubule networks. The N terminus of COMMD5 binds to the endosomal Rab5, and its C terminus, including the COMMD domain, binds to the cytoskeletal scaffolding. COMMD5 participates in long-range endosome transport, including epidermal growth factor receptor (EGFR) recycling, and provides the strength to deform and assist the scission of vesicles into sorting endosomes. This study establishes the molecular mechanism by which COMMD5 acts as an adaptor protein to coordinate endosomal trafficking and reveals its important role for EGFR transport and activity.
COMMD5/HCaRG 参与组织修复，其低表达与致瘤性有关。细胞的生长、迁移和分化受 COMMD5 控制。我们之前的研究表明，COMMD5 通过调节 ErbB 家族成员的表达或磷酸化来抑制肾癌细胞的生长。在这里，我们证明 COMMD5 对细胞骨架的稳定性至关重要。其沉默导致肌动蛋白和微管网络的主要重新组织。COMMD5 的 N 端与内体 Rab5 结合，其 C 端，包括 COMMD 结构域，与细胞骨架支架结合。COMMD5 参与长距离内体运输，包括表皮生长因子受体 (EGFR) 的回收，并提供变形的强度并协助将囊泡切成分选内体。本研究建立了 COMMD5 作为衔接蛋白协调内体运输的分子机制，并揭示了其对 EGFR 运输和活性的重要作用。
