Involvement of sphingosine 1-phosphate signaling in insulin-like growth factor-II/mannose 6-phosphate receptor trafficking from endosome to the trans-Golgi network

• Published in: Communications biology Vol. 7; no. 1; pp. 1182 - 13
• Main Authors: Nishida, Susumu, Matovelo, Shubi Ambwene, Kajimoto, Taketoshi, Nakamura, Shun-ichi, Okada, Taro
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 19.09.2024; Nature Publishing Group; Nature Portfolio
• Subjects: 13; 13/1; 13/95; 631/80/313/1624; 631/80/86/2365; 96; 96/1; 96/63; Adaptor proteins; Biomedical and Life Sciences; Casein; Casein kinase II; Cell surface; Endosomes; Endosomes - metabolism; Humans; Insulin; Insulin-like growth factor II; Insulin-Like Growth Factor II - metabolism; Insulin-like growth factors; Insulin-Like Peptides; Kinases; Life Sciences; Lysophospholipids - metabolism; Lysosomal enzymes; Lysosomes; Mannose; Molecular modelling; Protein Transport; Protein turnover; Receptor, IGF Type 2 - metabolism; Retrograde transport; Signal Transduction; Sphingosine - analogs & derivatives; Sphingosine - metabolism; Sphingosine 1-phosphate; trans-Golgi Network - metabolism
• ISSN: 2399-3642; 2399-3642
• DOI: 10.1038/s42003-024-06828-9

The insulin-like growth factor II/mannose 6-phosphate (IGF-II/M6P) receptor is a multifunctional glycoprotein not only play roles in IGF-II degradation and pro-TGFβ activation but binding to and transport M6P-bearing lysosomal enzymes from the trans-Golgi network (TGN) or the cell surface to lysosomes. At present, information regarding a retrograde transport of IGF-II/M6P receptor from endosomes to the TGN is still limited. We show here that a continuous ligand-dependent activation of sphingosine 1-phosphate receptor type 3 (S1P 3 R) on the endosomal membranes is required for subsequent recycling back of cargo-unloaded IGF-II/M6P receptors to the TGN. We have further clarified that Gq coupled with S1P 3 R plays a critical role in the activation of casein kinase 2, which phosphorylates and keeps PACS1 connector protein active for the association with IGF-II/M6P receptors, which enables transport carrier formation with the aid of other adaptor proteins toward the TGN. These findings shed light on the molecular mechanism underlying how continuous activation of the S1P receptor and subsequent downstream Gq signaling regulates the retrograde transport of the empty IGF-II/M6P receptors back to the TGN. Continuous activation of the sphingosine 1-phosphate (S1P) receptor 3 (S1P3R) and subsequent downstream Gq signaling in the endosomes regulate the retrograde transport of the IGF-II/M6P receptors back to the TGN.