title: Novel tyrosine phosphorylated and cardiolipin-binding protein CLPABP functions as mitochondrial RNA granule.
abstract: We identified a new protein containing the pleckstrin homology (PH) domain through tyrosine phosphoproteomics using epidermal growth factor-stimulated cells. The tandem PH domains of this protein can bind to mitochondria-specific phospholipid, cardiolipin or its dehydro product, phosphatidic acid; therefore, we have designated this protein as cardiolipin and phosphatidic acid-binding protein (CLPABP). In this study, we show that CLPABP is localized on the tubulin network and the mitochondrial surface in the granular form along with other proteins and RNA. The affinity of CLPABP to mitochondria is elevated depending on the extent of tyrosine phosphorylation. The CLPABP complex contains various proteins related to cytoplasmic mRNA metabolism. The unique subcellular localization of CLPABP requires its PH domains and a multifunctional protein, SF2p32, as its binding protein. The CLPABP granule also contains the cytochrome c transcript, which may be mediated by the RNA-binding protein HuR. Immunofluorescence staining reveals that the CLPABP granule is colocalized with cytochrome c and various ribosomal proteins that are present in the CLPABP complex. Therefore, the CLPABP RNA-protein complex may play a role in transporting cytochrome c mRNA and its translated product to the mitochondria.
authors.affiliation: Institute for Enzyme Research, The University of Tokushima, Tokushima 770-8503, Japan.
authors.forename: Etsuko
authors.initials: E
authors.lastname: Sano
authors.forename: Shigeichi
authors.initials: S
authors.lastname: Shono
authors.forename: Kyoko
authors.initials: K
authors.lastname: Tashiro
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Konishi
authors.forename: Emiko
authors.initials: E
authors.lastname: Yamauchi
authors.forename: Hisaaki
authors.initials: H
authors.lastname: Taniguchi
mesh_terms: D000818:Animals; D000954:Antigens, Surface / Q000378:metabolism; D017209:Apoptosis; D019556:COS Cells; D002308:Cardiolipins / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D045304:Cytochromes c / Q000378:metabolism; D003594:Cytoplasmic Granules / Q000378:metabolism; D051959:ELAV Proteins; D000067780:ELAV-Like Protein 1; D005455:Fluorescent Antibody Technique; D006801:Humans; D058635:Lipid-Linked Proteins; D008928:Mitochondria / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000378:metabolism; D010712:Phosphatidic Acids / Q000378:metabolism; D010766:Phosphorylation; D012313:RNA / Q000235:genetics / Q000378:metabolism*; D000077278:RNA, Mitochondrial; D016601:RNA-Binding Proteins / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012269:Ribosomal Proteins / Q000378:metabolism; D014162:Transfection; D014404:Tubulin / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism*
chemical_list: D000954:Antigens, Surface; C087299:C1QBP protein, human; D002308:Cardiolipins; D002352:Carrier Proteins; D051959:ELAV Proteins; D000067780:ELAV-Like Protein 1; C098770:ELAVL1 protein, human; D058635:Lipid-Linked Proteins; D024101:Mitochondrial Proteins; C530405:PLEKHN1 protein, human; D010712:Phosphatidic Acids; D000077278:RNA, Mitochondrial; D016601:RNA-Binding Proteins; D012269:Ribosomal Proteins; D014404:Tubulin; D014443:Tyrosine; D012313:RNA; D045304:Cytochromes c