title: Selective export of autotaxin from the endoplasmic reticulum.
abstract: Autotaxin (ATX) or ectonucleotide pyrophosphatase/phosphodiesterase 2 (ENPP2) is a secretory glycoprotein and functions as the key enzyme for lysophosphatidic acid generation. The mechanism of ATX protein trafficking is largely unknown. Here, we demonstrated that p23, a member of the p24 protein family, was the protein-sorting receptor required for endoplasmic reticulum (ER) export of ATX. A di-phenylalanine (Phe-838/Phe-839) motif in the human ATX C-terminal region was identified as a transport signal essential for the ATX-p23 interaction. Knockdown of individual Sec24 isoforms by siRNA revealed that ER export of ATX was impaired only if Sec24C was down-regulated. These results suggest that ATX is selectively exported from the ER through a p23, Sec24C-dependent pathway. In addition, it was found that AKT signaling played a role in ATX secretion regulation to facilitate ATX ER export by enhancing the nuclear factor of activated T cell-mediated p23 expression. Furthermore, the di-hydrophobic amino acid motifs (FY) also existed in the C-terminal regions of human ENPP1 and ENPP3. Such a p23, Sec24C-dependent selective ER export mechanism is conserved among these ENPP family members.
authors.affiliation: From the Key Laboratory of Cell Proliferation and Regulation Biology, Ministry of Education, Institute of Cell Biology, College of Life Sciences, Beijing Normal University, Beijing 100875, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Lyu
authors.affiliation: From the Key Laboratory of Cell Proliferation and Regulation Biology, Ministry of Education, Institute of Cell Biology, College of Life Sciences, Beijing Normal University, Beijing 100875, China.
authors.forename: Baolu
authors.initials: B
authors.lastname: Wang
authors.affiliation: From the Key Laboratory of Cell Proliferation and Regulation Biology, Ministry of Education, Institute of Cell Biology, College of Life Sciences, Beijing Normal University, Beijing 100875, China.
authors.forename: Chaoyang
authors.initials: C
authors.lastname: Xiong
authors.affiliation: From the Key Laboratory of Cell Proliferation and Regulation Biology, Ministry of Education, Institute of Cell Biology, College of Life Sciences, Beijing Normal University, Beijing 100875, China.
authors.forename: Xiaotian
authors.initials: X
authors.lastname: Zhang
authors.affiliation: From the Key Laboratory of Cell Proliferation and Regulation Biology, Ministry of Education, Institute of Cell Biology, College of Life Sciences, Beijing Normal University, Beijing 100875, China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Zhang
authors.affiliation: From the Key Laboratory of Cell Proliferation and Regulation Biology, Ministry of Education, Institute of Cell Biology, College of Life Sciences, Beijing Normal University, Beijing 100875, China jjzhang@bnu.edu.cn.
authors.forename: Junjie
authors.initials: J
authors.lastname: Zhang
mesh_terms: D020816:Amino Acid Motifs; D002467:Cell Nucleus / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D006367:HeLa Cells; D006801:Humans; D008246:Lysophospholipids / Q000378:metabolism; D008856:Microscopy, Fluorescence; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism*; D011485:Protein Binding; D000072417:Protein Domains; D021381:Protein Transport; D011755:Pyrophosphatases / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D015398:Signal Transduction; D033921:Vesicular Transport Proteins / Q000378:metabolism; D000099189:Lysophospholipase D
chemical_list: D008246:Lysophospholipids; D010727:Phosphoric Diester Hydrolases; D011755:Pyrophosphatases; D034741:RNA, Small Interfering; D033921:Vesicular Transport Proteins; D000099189:Lysophospholipase D; C427944:ENPP3 protein, human; C530638:SEC24A protein, human; C530639:SEC24B protein, human; C530640:SEC24C protein, human; C530641:SEC24D protein, human; C065962:ectonucleotide pyrophosphatase phosphodiesterase 1; C032881:lysophosphatidic acid
keywords: COPII; ENPP family; ER export; Sec24C; autotaxin; endoplasmic reticulum (ER); lysophospholipid; p23; protein sorting; receptor