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昼夜生理节律使得生物体的生理和行为能够适应外界环境的昼夜循环变化. 实验发现在果蝇的细胞质中存在由PER-TIM复合体组成的间隔计时器. 本文提出了这个间隔定时器的一种可能的数学模型. 模型的特点是大聚合物, 快速交换, 不同磷酸化位点有不同功能. 模拟结果基本与实验相符, 符合PER-TIM间隔定时器的主要时间特征并重现了perL 变异细胞系中定时器的特点, 以及PER和TIM蛋白进入细胞核的三种不同类型的过程.
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关键词:
- PER-TIM生物钟 /
- 间隔计时器 /
- 翻译后调控
Circadian rhythm makes physiology and behaviors of organisms adapt to the day and night cycle in the environment. Recent experiment indicated a PER-TIM interval timer in Drosophila melanogaster cytoplasm. In this paper, we present a possible mathematical model for this interval timer. The characters of the model are the formation of big clusters, fast exchange and different functions of phosphorylation of different sites. The experimental results on features of the PER-TIM interval timer of mild type and perL mutant and on the existence of three different types of temporal profiles of nuclear accumulation of PER and TIM in single cells are reproduced by our simulations.-
Keywords:
- PER-TIM /
- circadian clock /
- interval timer
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[5] Williams J, A Sehgal A 2001 Annu. Rev. Physiol. 63 729
[6] Gallego M, Virshup D M 2007 Nat. Rev. Mol. Cell Biol. 8 139
[7] Emberly E, Wingreen N 2006 Phys. Rev. Lett. 96 038303
[8] Tomita J, Nakajima M, Kondo T, Iwasaki H 2005 Science 307 251
[9] Nakajima M, Imai K, Ito H, Nishiwaki T, Murayama Y, Iwasaki H, Oyama T, Kondo T 2005 Science 308 414
[10] Li C, Chen X, Wang P, Wang W 2009 PLoS Comput. Biol. 5 e1000568
[11] Curtin K D, Huang Z J, Rosbash M 1995 Neuron 14 365
[12] Sehgal A, Rothenfluh-Hilfiker A, Hunter-Ensor M, Chen Y, Myers M P, Young M W 1995 Science 270 808
[13] Gekakis N, Saez L, Delahaye-Brown A M, Myers M P, Sehgal A, Young M W, Weitz C J 1995 Science 270 811
[14] Allada R, Emery P, Takahashi J S, Rosbash M 2001 Annu. Rev. Neurosci. 24 1091
[15] Meyer P 2006 Science 311 226
[16] Kuczenski R S, Hong K C, Garcia-Ojalvo J, Lee K H 2007 PLoS Comput. Biol. 3 e154
[17] Holmberg C I, Tran S E, Eriksson J E, Sistonen L 2002 Trends Biochem. Sci. 27 619
[18] Ermentrout B, Mahajan A 2003 APPL. MECH. REV. 56 B53
[19] Shafer O T, Rosbash M, Truman J W 2002 J. Neurosci. 22 5946
[20] Kivimae S, Saez L, Young M W 2008 PLoS Biol. 6 e183
[21] Fang Y, Sathyanarayanan S, Sehgal A 2007 Genes Dev. 21 1506
[22] Schlosser A, Vanselow J T, Kramer A 2005 Anal. Chem. 77 5243
[23] Park K S, Mohapatra D P, Misonou H, Trimmer J S 2006 Science 313 976
[24] Wu R C, Qin J, Yi P, Wong J, Tsai S Y, Tsai M J, O'Malley B W 2004 Mol. Cell 15 937
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[1] Bell-Pedersen D, Cassone V M, Earnest D J, Golden S S, Hardin P E, Thomas T L, Zoran M J 2005 Nat. Rev. Genet. 6 544
[2] Allada R, Chung B Y 2010 Annu. Rev. Physiol. 72 605
[3] Rutter J, Reick M, McKnight S L 2002 Annu. Rev. Biochem. 71 307
[4] Levi F, Schibler U 2007 Ann. Rev. Pharmacol. Toxicol. 47 593
[5] Williams J, A Sehgal A 2001 Annu. Rev. Physiol. 63 729
[6] Gallego M, Virshup D M 2007 Nat. Rev. Mol. Cell Biol. 8 139
[7] Emberly E, Wingreen N 2006 Phys. Rev. Lett. 96 038303
[8] Tomita J, Nakajima M, Kondo T, Iwasaki H 2005 Science 307 251
[9] Nakajima M, Imai K, Ito H, Nishiwaki T, Murayama Y, Iwasaki H, Oyama T, Kondo T 2005 Science 308 414
[10] Li C, Chen X, Wang P, Wang W 2009 PLoS Comput. Biol. 5 e1000568
[11] Curtin K D, Huang Z J, Rosbash M 1995 Neuron 14 365
[12] Sehgal A, Rothenfluh-Hilfiker A, Hunter-Ensor M, Chen Y, Myers M P, Young M W 1995 Science 270 808
[13] Gekakis N, Saez L, Delahaye-Brown A M, Myers M P, Sehgal A, Young M W, Weitz C J 1995 Science 270 811
[14] Allada R, Emery P, Takahashi J S, Rosbash M 2001 Annu. Rev. Neurosci. 24 1091
[15] Meyer P 2006 Science 311 226
[16] Kuczenski R S, Hong K C, Garcia-Ojalvo J, Lee K H 2007 PLoS Comput. Biol. 3 e154
[17] Holmberg C I, Tran S E, Eriksson J E, Sistonen L 2002 Trends Biochem. Sci. 27 619
[18] Ermentrout B, Mahajan A 2003 APPL. MECH. REV. 56 B53
[19] Shafer O T, Rosbash M, Truman J W 2002 J. Neurosci. 22 5946
[20] Kivimae S, Saez L, Young M W 2008 PLoS Biol. 6 e183
[21] Fang Y, Sathyanarayanan S, Sehgal A 2007 Genes Dev. 21 1506
[22] Schlosser A, Vanselow J T, Kramer A 2005 Anal. Chem. 77 5243
[23] Park K S, Mohapatra D P, Misonou H, Trimmer J S 2006 Science 313 976
[24] Wu R C, Qin J, Yi P, Wong J, Tsai S Y, Tsai M J, O'Malley B W 2004 Mol. Cell 15 937
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