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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 저널정보
- 대한약리학회 The Korean Journal of Physiology & Pharmacology The Korean Journal of Physiology & Pharmacology 제23권 제6호
- 발행연도
- 2019.1
- 수록면
- 539 - 547 (9page)
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초록· 키워드
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Anoctamin 5 (ANO5)/TMEM16E belongs to a member of the ANO/ TMEM16 family member of anion channels. However, it is a matter of debate whether ANO5 functions as a genuine plasma membrane chloride channel. It has been recognized that mutations in the ANO5 gene cause many skeletal muscle diseases such as limb girdle muscular dystrophy type 2L (LGMD2L) and Miyoshi muscular dystrophy type 3 (MMD3) in human. However, the molecular mechanisms of the skeletal myopathies caused by ANO5 defects are poorly understood. To understand the role of ANO5 in skeletal muscle development and function, we silenced the ANO5 gene in C2C12 myoblasts and evaluated whether it impairs myogenesis and myotube function. ANO5 knockdown (ANO5-KD) by shRNA resulted in clustered or aggregated nuclei at the body of myotubes without affecting differentiation or myotube formation. Nuclear positioning defect of ANO5-KD myotubes was accompanied with reduced expression of Kif5b protein, a kinesin-related motor protein that controls nuclear transport during myogenesis. ANO5-KD impaired depolarization-induced [Ca2+]i transient and reduced sarcoplasmic reticulum (SR) Ca2+ storage. ANO5-KD resulted in reduced protein expression of the dihydropyridine receptor (DHPR) and SR Ca2+-ATPase subtype 1. In addition, ANO5-KD compromised co-localization between DHPR and ryanodine receptor subtype 1. It is concluded that ANO5-KD causes nuclear positioning defect by reduction of Kif5b expression, and compromises Ca2+ signaling by downregulating the expression of DHPR and SERCA proteins.
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참고문헌 (24)
참고문헌 신청
Pedemonte N / 2014 / Structure and function of TMEM16 proteins(anoctamins) / Physiol Rev 94:419~459
Yang YD / 2008 / TMEM16A confers receptor-activated calcium-dependent chloride conductance / Nature 455:1210~1215
Stephan AB / 2009 / ANO2 is the cilial calcium-activated chloride channel that may mediate olfactory amplification / Proc Natl Acad Sci U S A 106:11776~11781
Tian Y / 2012 / Anoctamins are a family of Ca2+-activated Cl- channels / J Cell Sci 125(Pt 21):4991~4998
Duran C / 2012 / ANOs 3-7 in the anoctamin/Tmem16 Cl-channel family are intracellular proteins / Am J Physiol Cell Physiol 302:C482~C493
Yang YD / 2008 / TMEM16A confers receptor-activated calcium-dependent chloride conductance / Nature 455:1210~1215
Stephan AB / 2009 / ANO2 is the cilial calcium-activated chloride channel that may mediate olfactory amplification / Proc Natl Acad Sci U S A 106:11776~11781
Tian Y / 2012 / Anoctamins are a family of Ca2+-activated Cl- channels / J Cell Sci 125(Pt 21):4991~4998
Duran C / 2012 / ANOs 3-7 in the anoctamin/Tmem16 Cl-channel family are intracellular proteins / Am J Physiol Cell Physiol 302:C482~C493
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