N termini of apPDE4 isoforms are responsible for targeting the isoforms to different cellular membranes

Jang, Deok‐Jin; Park, Soowon; Lee, Jina; Lee, Chang‐Hoon; Chae, Yeon-Su; Park, Hyungju; Kim, Minjeong; Choi, Sun-Lim; Lee, Nuribalhae; Kim, Hyoung; Kaang, Bong‐Kiun

doi:10.1101/lm.1899410

Cited by 19 publications

(43 citation statements)

References 39 publications

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“…Unlike the mammalian PDE4 short form, the ApPDE4 short form contains an NTR, UCR2, and truncated UCR1 (the C-terminal half. We also described that the ApPDE4 short and long forms were localized to the plasma membrane and to both the plasma membrane and presynaptic terminals, respectively (8). However, the molecular mechanisms of the distinct membrane targeting of the ApPDE4 long and short forms was not clear.…”

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confidence: 99%

“…Because the NTR-UCR1-2 of the ApPDE4 long form was sufficient for its subcellular targeting (7,8), enhanced GFP (EGFP) was fused to the C-terminal region of NTR-UCR1-2 to create L(N-UCR1-2)-EGFP and expressed in HEK293T cells. As shown in Fig.…”

Section: Intracellular Localization Of the Appde4 Long And Shortmentioning

confidence: 99%

“…The NTR of PDE4A1, a brainspecific isoform, is known to be the only PDE4 isoform that interacts with the membrane directly and is targeted to the Golgi complex and its associated vesicles through the two helices (helices 1 and 2) within the NTR (21,22). Recently, we showed that the NTRs of the ApPDE4 long and short forms might be involved in intracellular membrane targeting, probably through lipid binding (8).…”

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confidence: 99%

“…A mutation of dunce encoding a Drosophila PDE4 isoform impaired synaptic facilitation and olfactory learning (4 -6). In Aplysia, knockdown of the Aplysia PDE4s (ApPDE4s) impaired 5-HT-induced synaptic facilitation (7,8), and overexpression of the ApPDE4 supershort form impaired 5-HT-induced synaptic facilitation in a non-de-pressed, but not in a depressed, synapse (9). In mammals, treatment with a PDE4-specific inhibitor, rolipram, enhanced performances in hippocampus-dependent memory tasks such as context-dependent fear conditioning and the object recognition task (10,11).…”

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confidence: 99%

“…We previously cloned all three isoforms of ApPDE4, which are mammalian PDE4D homologues (7,8). Unlike the mammalian PDE4 short form, the ApPDE4 short form contains an NTR, UCR2, and truncated UCR1 (the C-terminal half.…”

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confidence: 99%

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Intracellular Membrane Association of the Aplysia cAMP Phosphodiesterase Long and Short Forms via Different Targeting Mechanisms

Kim

Jun

Park

et al. 2014

Journal of Biological Chemistry

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Background: Phosphodiesterases play a role in cAMP regulation through specific targeting. Results: Membrane targeting of the Aplysia phosphodiesterase long and short forms is mediated hydrophobically and electrostatically, respectively. Conclusion:The Aplysia phosphodiesterase long and short forms are targeted to the intracellular membranes by different mechanisms. Significance: This is the first report demonstrating that phosphodiesterase is targeted to the membranes by hydrophobic or electrostatic interactions.

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Section: Intracellular Localization Of the Appde4 Long And Shortmentioning

confidence: 99%

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confidence: 99%

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confidence: 99%

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confidence: 99%

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Intracellular Membrane Association of the Aplysia cAMP Phosphodiesterase Long and Short Forms via Different Targeting Mechanisms

Kim

Jun

Park

et al. 2014

Journal of Biological Chemistry

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Proteomic characterization of the abdominal ganglion of Aplysia californica—A protein resource for neuroscience

et al. 2012

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Aplysia californica (AC) is a widely used model for testing learning and memory. Although ESTs have been generated, proteomics studies on AC proteins are limited. Studies at the protein level, however, are mandatory, not only due to the fact that studies at the nucleic acid level are not allowing conclusions about PTMs. A gel-based proteomics method was therefore applied to carry out protein profiling in abdominal ganglia from AC. Abdominal ganglia were extirpated, proteins extracted and run on 2DE with subsequent in-gel digestion with trypsin, chymotrypsin, and partially by subtilisin. Peptides were identified using a nano-LC-ESI-LTQ-FT-mass spectrometer. MS/MS data were analyzed by searching the NCBI nonredundant public AC EST database and the NCBI nonredundant public AC protein database. A total of 477 different proteins represented by 363 protein spots were detected and were assigned to different protein pathways as for instance signaling (receptors, protein kinases, and phosphatases), metabolism, protein synthesis, handling and degradation, cytoskeleton and structural, oxido-redox, heat shock and chaperone, hypothetical, predicted and unnamed proteins. The generation of a protein map of soluble proteins shows the existence of so far hypothetical and predicted proteins and is allowing and challenging further work at the protein level, in particular in the field of neuroscience.

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The Past, Present, and Future of Phosphodiesterase-4 Modulation for Age-Induced Memory Loss

Hansen

Zhang

2017

Advances in Neurobiology

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The purpose of this chapter is to highlight the state of progress for phosphodiesterase-4 (PDE4) modulation as a potential therapeutic for psychiatric illness, and to draw attention to particular hurdles and obstacles that must be overcome in future studies to develop PDE4-mediated therapeutics. Pathological and non-pathological related memory loss will be the focus of the chapter; however, we will at times also touch upon other psychiatric illnesses like anxiety and depression. First, we will provide a brief background of PDE4, and the rationale for its extensive study in cognition. Second, we will explore fundamental differences in individual PDE4 subtypes, and then begin to address differences between pathological and non-pathological aging. Alterations of cAMP/PDE4 signaling that occur within normal vs. pathological aging, and the potential for PDE4 modulation to combat these alterations within each context will be described. Finally, we will finish the chapter with obstacles that have hindered the field, and future studies and alternative viewpoints that need to be addressed. Overall, we hope this chapter will demonstrate the incredible complexity of PDE4 signaling in the brain, and will be useful in forming a strategy to develop future PDE4-mediated therapeutics for psychiatric illnesses.

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N termini of apPDE4 isoforms are responsible for targeting the isoforms to different cellular membranes

Cited by 19 publications

References 39 publications

Intracellular Membrane Association of the Aplysia cAMP Phosphodiesterase Long and Short Forms via Different Targeting Mechanisms

Intracellular Membrane Association of the Aplysia cAMP Phosphodiesterase Long and Short Forms via Different Targeting Mechanisms

Proteomic characterization of the abdominal ganglion of Aplysia californica—A protein resource for neuroscience

The Past, Present, and Future of Phosphodiesterase-4 Modulation for Age-Induced Memory Loss

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