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학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 저널정보
- 대한약리학회 The Korean Journal of Physiology & Pharmacology The Korean Journal of Physiology & Pharmacology 제24권 제3호
- 발행연도
- 2020.1
- 수록면
- 277 - 286 (10page)
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초록· 키워드
오류제보하기
Polycystic kidney disease 2-like-1 (PKD2L1), also known as polycystin- L or TRPP3, is a non-selective cation channel that regulates intracellular calcium concentration. Calmodulin (CaM) is a calcium binding protein, consisting of N-lobe and C-lobe with two calcium binding EF-hands in each lobe. In previous study, we confirmed that CaM is associated with desensitization of PKD2L1 and that CaM Nlobe and PKD2L1 EF-hand specifically are involved. However, the CaM-binding domain (CaMBD) and its inhibitory mechanism of PKD2L1 have not been identified. In order to identify CaM-binding anchor residue of PKD2L1, single mutants of putative CaMBD and EF-hand deletion mutants were generated. The current changes of the mutants were recorded with whole-cell patch clamp. The calmidazolium (CMZ), a calmodulin inhibitor, was used under different concentrations of intracellular. Among the mutants that showed similar or higher basal currents with that of the PKD2L1 wild type, L593A showed little change in current induced by CMZ. Co-expression of L593A with CaM attenuated the inhibitory effect of PKD2L1 by CaM. In the previous study it was inferred that CaM C-lobe inhibits channels by binding to PKD2L1 at 16 nM calcium concentration and CaM N-lobe at 100 nM. Based on the results at 16 nM calcium concentration condition, this study suggests that CaM C-lobe binds to Leu- 593, which can be a CaM C-lobe anchor residue, to regulate channel activity. Taken together, our results provide a model for the regulation of PKD2L1 channel activity by CaM.
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참고문헌 (35)
참고문헌 신청
Delling M / 2013 / Primary cilia are specialized calcium signalling organelles / Nature 504:311~314
Sternberg JR / 2018 / Pkd2l1 is required for mechanoception in cerebrospinal fluid-contacting neurons and maintenance of spine curvature / Nat Commun 9:3804
DeCaen PG / 2013 / Direct recording and molecular identification of the calcium channel of primary cilia / Nature 504:315~318
Ishimaru Y / 2006 / Transient receptor potential family members PKD1L3 and PKD2L1 form a candidate sour taste receptor / Proc Natl Acad Sci U S A 103:12569~12574
Zheng W / 2015 / A novel PKD2L1 C-terminal domain critical for trimerization and channel function / Sci Rep 5:9460
Sternberg JR / 2018 / Pkd2l1 is required for mechanoception in cerebrospinal fluid-contacting neurons and maintenance of spine curvature / Nat Commun 9:3804
DeCaen PG / 2013 / Direct recording and molecular identification of the calcium channel of primary cilia / Nature 504:315~318
Ishimaru Y / 2006 / Transient receptor potential family members PKD1L3 and PKD2L1 form a candidate sour taste receptor / Proc Natl Acad Sci U S A 103:12569~12574
Zheng W / 2015 / A novel PKD2L1 C-terminal domain critical for trimerization and channel function / Sci Rep 5:9460
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