title: Ubiquitination and dynactin regulate TMEPAI lysosomal trafficking.
abstract: The transmembrane prostate androgen-induced protein (TMEPAI) has been reported to be elevated in various tumor cells, is localized to the lysosome and promotes lysosome stability. The molecular mechanism of TMEPAI trafficking however to the lysosome is unknown. Here we report that clathrin and CI-M6PR mediate TMEPAI transport from the Golgi directly into the endo-lysosomal pathway. TMEPAI is ubiquitinated at its C-terminal region and ubiquitination modification of TMEPAI is a signal for its lysosomal trafficking. Moreover, TMEPAI binds the ubiquitin binding proteins Hrs and STAM which is required for its lysosomal transport. In addition, TMEPAI interacts with the dynactin pointed-end complex subunits dynactin 5 and dynactin 6. The aa 132-155 domain is essential for specific TMEPAI binding and deletion of this binding site leads to mis-trafficking of TMEPAI to the plasma membrane. These results reveal the pathway and mechanism regulating transport of TMEPAI to the lysosome, which helps to further understand the role of TMEPAI in tumorigenesis.
authors.affiliation: School of Biotechnology, Tianjin University of Science and Technology, Key Lab of Industrial Fermentation Microbiology of the Ministry of Education, Tianjin, 300457, China.
authors.forename: Shenheng
authors.initials: S
authors.lastname: Luo
authors.affiliation: School of Biotechnology, Tianjin University of Science and Technology, Key Lab of Industrial Fermentation Microbiology of the Ministry of Education, Tianjin, 300457, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Jing
authors.affiliation: School of Biotechnology, Tianjin University of Science and Technology, Key Lab of Industrial Fermentation Microbiology of the Ministry of Education, Tianjin, 300457, China.
authors.forename: Tian
authors.initials: T
authors.lastname: Zhao
authors.affiliation: School of Biotechnology, Tianjin University of Science and Technology, Key Lab of Industrial Fermentation Microbiology of the Ministry of Education, Tianjin, 300457, China.
authors.forename: Yuyin
authors.initials: Y
authors.lastname: Li
authors.affiliation: School of Biotechnology, Tianjin University of Science and Technology, Key Lab of Industrial Fermentation Microbiology of the Ministry of Education, Tianjin, 300457, China.
authors.forename: Zhenxing
authors.initials: Z
authors.lastname: Liu
authors.affiliation: School of Biotechnology, Tianjin University of Science and Technology, Key Lab of Industrial Fermentation Microbiology of the Ministry of Education, Tianjin, 300457, China.
authors.forename: Aipo
authors.initials: A
authors.lastname: Diao
mesh_terms: D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D002966:Clathrin / Q000378:metabolism; D000072159:Dynactin Complex / Q000378:metabolism*; D006056:Golgi Apparatus / Q000378:metabolism; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism; D008247:Lysosomes / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D021381:Protein Transport; D017527:Receptor, IGF Type 2 / Q000378:metabolism; D054875:Ubiquitination
chemical_list: D002966:Clathrin; D000072159:Dynactin Complex; D008565:Membrane Proteins; C412868:PMEPA1 protein, human; D017527:Receptor, IGF Type 2; C034304:cation-dependent mannose-6-phosphate receptor