title: The hydrophobic amino acids involved in the interdomain association of phospholipase D1 regulate the shuttling of phospholipase D1 from vesicular organelles into the nucleus.
abstract: Phospholipase D (PLD) catalyzes the hydrolysis of phosphatidylcholine to generate the lipid second messenger, phosphatidic acid. PLD is localized in most cellular organelles, where it is likely to play different roles in signal transduction. PLD1 is primarily localized in vesicular structures such as endosomes, lysosomes and autophagosomes. However, the factors defining its localization are less clear. In this study, we found that four hydrophobic residues present in the N-terminal HKD catalytic motif of PLD1, which is involved in intramolecular association, are responsible for vesicular localization. Site-directed mutagenesis of the residues dramatically disrupted vesicular localization of PLD1. Interestingly, the hydrophobic residues of PLD1 are also involved in the interruption of its nuclear localization. Mutation of the residues increased the association of PLD1 with importin-β, which is known to mediate nuclear importation, and induced the localization of PLD1 from vesicles into the nucleus. Taken together, these data suggest that the hydrophobic amino acids involved in the interdomain association of PLD1 are required for vesicular localization and disturbance of its nuclear localization.
authors: Department of Molecular Biology College of Natural Science Pusan National University Busan 609-735, Korea.
authors: Young Hoon
authors: YH
authors: Jang
authors: Do Sik
authors: do S
authors: Min
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000596:Amino Acids / Q000737:chemistry; D002467:Cell Nucleus / Q000201:enzymology*; D011992:Endosomes / Q000201:enzymology; D057809:HEK293 Cells; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008247:Lysosomes / Q000201:enzymology; D010588:Phagosomes / Q000201:enzymology; D010739:Phospholipase D / Q000737:chemistry / Q000378:metabolism*; D054730:Protein Interaction Domains and Motifs; D021381:Protein Transport; D022161:Transport Vesicles / Q000201:enzymology*
chemical_list: D000596:Amino Acids; D010739:Phospholipase D; C106801:phospholipase D1