title: Intracellular membrane association of the Aplysia cAMP phosphodiesterase long and short forms via different targeting mechanisms.
abstract: Phosphodiesterases (PDEs) play key roles in cAMP compartmentalization, which is required for intracellular signaling processes, through specific subcellular targeting. Previously, we showed that the long and short forms of Aplysia PDE4 (ApPDE4), which are localized to the membranes of distinct subcellular organelles, play key roles in 5-hydroxytryptamine-induced synaptic facilitation in Aplysia sensory and motor synapses. However, the molecular mechanism of the isoform-specific distinct membrane targeting was not clear. In this study, we further investigated the molecular mechanism of the membrane targeting of the ApPDE4 long and short forms. We found that the membrane targeting of the long form was mediated by hydrophobic interactions, mainly via 16 amino acids at the N-terminal region, whereas the short form was targeted solely to the plasma membrane, mainly by nonspecific electrostatic interactions between their N termini and the negatively charged lipids such as the phosphatidylinositol polyphosphates PI4P and PI(4,5)P2, which are embedded in the inner leaflet of the plasma membrane. Moreover, oligomerization of the long or short form by interaction of their respective upstream conserved region domains, UCR1 and UCR2, enhanced their plasma membrane targeting. These results suggest that the long and short forms of ApPDE4 are distinctly targeted to intracellular membranes through their direct association with the membranes via hydrophobic and electrostatic interactions, respectively.
authors: From the Department of Ecological Science, College of Ecology and Environment, Kyungpook National University, 386, Gajang-dong, Sangju-si, Kyungbuk 742-711, Korea.
authors: Kun-Hyung
authors: KH
authors: Kim
authors: From the Department of Ecological Science, College of Ecology and Environment, Kyungpook National University, 386, Gajang-dong, Sangju-si, Kyungbuk 742-711, Korea.
authors: Yong-Woo
authors: YW
authors: Jun
authors: the Department of Neurobiology, Max-Planck-Institute for Biophysical Chemistry, Am Fassberg 11, 37077 Göttingen, Germany.
authors: Yongsoo
authors: Y
authors: Park
authors: the Department of Biotechnology, College of Life Science and Nanotechnology, Hannam University, 461-6, Jeonmin-dong, Yuseong-gu, Daejeon 305-811, Korea.
authors: Jin-A
authors: JA
authors: Lee
authors: the Department of Brain Science, Daegu Gyeongbuk Institute of Science and Technology (DGIST), Daegu 711-873, Korea.
authors: Byung-Chang
authors: BC
authors: Suh
authors: the Department of Biological Sciences, College of Natural Sciences, Seoul National University, 599 Gwanangno, Gwanak-gu, Seoul 151-747, Korea, and.
authors: Chae-Seok
authors: CS
authors: Lim
authors: the Department of Life Science, College of Natural Science, Chung-Ang University, Seoul 156-756, Korea.
authors: Yong-Seok
authors: YS
authors: Lee
authors: the Department of Biological Sciences, College of Natural Sciences, Seoul National University, 599 Gwanangno, Gwanak-gu, Seoul 151-747, Korea, and kaang@snu.ac.kr.
authors: Bong-Kiun
authors: BK
authors: Kaang
authors: From the Department of Ecological Science, College of Ecology and Environment, Kyungpook National University, 386, Gajang-dong, Sangju-si, Kyungbuk 742-711, Korea, jangdj@knu.ac.kr.
authors: Deok-Jin
authors: DJ
authors: Jang
mesh_terms: D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000235:genetics / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D001048:Aplysia / Q000201:enzymology*; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D007425:Intracellular Membranes / Q000187:drug effects; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism*; D055503:Protein Multimerization / Q000235:genetics; D012701:Serotonin / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D013569:Synapses / Q000235:genetics / Q000378:metabolism*
chemical_list: D020033:Protein Isoforms; D012701:Serotonin; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4
keywords: Aplysia; Electrostatic Interaction; Hydrophobic Interaction; Membrane; Oligomerization; Phosphodiesterases; Phosphoinositide; Plasma Membrane; Subcellular Organelle