지원사업
학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
커뮤니티
연구자들이 자신의 연구와 전문성을 널리 알리고, 새로운 협력의 기회를 만들 수 있는 네트워킹 공간이에요.
논문 기본 정보
- 자료유형
- 학위논문
- 저자정보
- 지도교수
- 장덕진.
- 발행연도
- 2014
- 저작권
- 경북대학교 논문은 저작권에 의해 보호받습니다.
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Phosphodiesterases (PDEs) play a key role in the compartmentalization of cAMP in cell-signaling processes through the specific intracellular targeting. Previously, I have showed that the short- and long-forms of ApPDE4 were distinctively localized to the plasma membrane only, and to both plasma membrane and presynaptic terminals in Aplysia sensory neurons, respectively. However, the molecular mechanism of the isoform-specific distinct membrane targeting was not clear. In this study, I deciphered the molecular mechanism of the isoform-specific localization further. Firstly, I found that the targeting of the long-form was mediated by hydrophobic interaction using in vitro liposome binding assay and various pharmacological approaches. On the other hand, the localization of the short-form was switched from plasma membrane to cytoplasm by changes in phosphoinositide contents following antimycin treatment or by changes of the charges in membrane surface followed by sphingosine treatment. Thus, I clearly showed that ApPDE4 long- and short-form were targeted to membranous organelles via distinct molecular mechanism by hydrophobic interaction and electrostatic interaction, respectively
목차
Ⅰ. Introduction……………………………………………1Ⅱ. Materials and methods…………………………………………………… 7DNA constructs……………………………………………7Cell culture…………………………………………………8Lipid-binding assay………………………………………………………8Immunocytochemistry…………………………………9Pharmacological treatments…………………………………………………9Rapamycin-inducible recruitment of the FKBP-PJ…………………………………………………………10Statistical Analyses……………………………………10Ⅲ. Result…………………………………………………12Cellular localization of ApPDE4 isoforms……………12Minimum region of membrane targeting of ApPDE4 isoforms……………………………………………………15ApPDE4 short-form but not long-form binds to acidic lipid…………………………………………………………19Membrane localization of ApPDE4 isoform by treatment of various pharmacological inhibitors……………………27Effect of an acute depletion of PIs on cellular localization of ApPDE4 isoforms…………………………………………37Ⅳ. Discussion …………………………………………44Ⅴ. References…………………………………………49국문초록
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