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ABBS: Intracellular trafficking of TGFbeta receptors

已有 2090 次阅读 2019-9-30 08:37 |个人分类:期刊新闻|系统分类:论文交流| TGF beta, receptor, signaling, trafficking

Intracellular trafficking of transforming growth factor β receptors

Ihor Yakymovych, Mariya Yakymovych, and Carl-Henrik Heldin

Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala 75123, Sweden

Acta Biochim Biophys Sin 2018, 50: 3–11; doi: 10.1093/abbs/gmx119

Transforming growth factor β (TGFβ) family members signal via heterotetrameric complexes of type I (TβRI) and type II (TβRII) dual specificity kinase receptors. The availability of the receptors on the cell surface is controlled by several mechanisms. Newly synthesized TβRI and TβRII are delivered from the Golgi apparatus to the cell surface via separate routes. On the cell surface, TGFβ receptors are distributed between different microdomains of the plasma membrane and can be internalized via clathrin- and caveolae-mediated endocytic mechanisms. Although receptor endocytosis is not essential for TGFβ signaling, localization of the activated receptor complexes on the early endosomes promotes TGFβ-induced Smad activation. Caveolae-mediated endocytosis, which is widely regarded as a mechanism that facilitates the degradation of TGFβ receptors, has been shown to be required for TGFβ signaling via non-Smad pathways. The importance of proper control of TGFβ receptor intracellular trafficking is emphasized by clinical data, as mislocalization of receptors has been described in connection with several human diseases. Thus, control of intracellular trafficking of the TGFβ receptors together with the regulation of their expression, posttranslational modifications and down-regulation, ensure proper regulation of TGFβ signaling.