TY - JOUR
T1 - Intracellular membrane association of the aplysia cAMP phosphodiesterase long and short forms via different targeting mechanisms
AU - Kim, Kun Hyung
AU - Jun, Yong Woo
AU - Park, Yongsoo
AU - Lee, Jin A.
AU - Suh, Byung Chang
AU - Lim, Chae Seok
AU - Lee, Yong Seok
AU - Kaang, Bong Kiun
AU - Jang, Deok Jin
N1 - Publisher Copyright:
© 2014 by The American Society for Biochemistry and Molecular Biology, Inc.
PY - 2014/9/12
Y1 - 2014/9/12
N2 - 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-hydroxytryptamineinduced 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 theirNtermini 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.
AB - 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-hydroxytryptamineinduced 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 theirNtermini 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.
UR - http://www.scopus.com/inward/record.url?scp=84907164523&partnerID=8YFLogxK
U2 - 10.1074/jbc.M114.572222
DO - 10.1074/jbc.M114.572222
M3 - Article
C2 - 25077971
AN - SCOPUS:84907164523
SN - 0021-9258
VL - 289
SP - 25797
EP - 25811
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 37
ER -