Negative regulation and gain control of sensory neurons by the C-elegans calcineurin TAX-6

被引:109
作者
Kuhara, A
Inada, H
Katsura, I
Mori, I [1 ]
机构
[1] Nagoya Univ, Japan Sci & Technol Corp, PRESTO, Nagoya, Aichi 4648602, Japan
[2] Nagoya Univ, Grad Sch Sci, Div Biol Sci, Nagoya, Aichi 4648602, Japan
[3] Natl Inst Genet, Struct Biol Ctr, Mishima, Shizuoka 4118540, Japan
关键词
D O I
10.1016/S0896-6273(02)00607-4
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Animals sense and adapt to variable environments by regulating appropriate sensory signal transduction pathways. Here, we show that calcineurin plays a key role in regulating the gain of sensory neuron responsiveness across multiple modalities. C. elegans animals bearing a loss-of-function mutation in TAX-6, a calcineurin A subunit, exhibit pleiotropic abnormalities, including many aberrant sensory behaviors. The tax-6 mutant defect in thermosensation is consistent with hyperactivation of the AFD thermosensory neurons. Conversely, constitutive activation of TAX-6 causes a behavioral phenotype consistent with inactivation of AFD neurons. In olfactory neurons, the impaired olfactory response of tax-6 mutants to an AWC-sensed odorant is caused by hyperadaptation, which is suppressible by a mutation causing defective olfactory adaptation. Taken together, our results suggest that stimulus-evoked calcium entry activates calcineurin, which in turn negatively regulates multiple aspects of sensory signaling.
引用
收藏
页码:751 / 763
页数:13
相关论文
共 56 条
[1]   THE STRUCTURE OF THE B-SUBUNIT OF CALCINEURIN [J].
AITKEN, A ;
KLEE, CB ;
COHEN, P .
EUROPEAN JOURNAL OF BIOCHEMISTRY, 1984, 139 (03) :663-671
[2]   CHEMOSENSORY NEURONS WITH OVERLAPPING FUNCTIONS DIRECT CHEMOTAXIS TO MULTIPLE CHEMICALS IN C-ELEGANS [J].
BARGMANN, CI ;
HORVITZ, HR .
NEURON, 1991, 7 (05) :729-742
[3]   ODORANT-SELECTIVE GENES AND NEURONS MEDIATE OLFACTION IN C-ELEGANS [J].
BARGMANN, CI ;
HARTWIEG, E ;
HORVITZ, HR .
CELL, 1993, 74 (03) :515-527
[4]   TRANSSPLICING AND POLYCISTRONIC TRANSCRIPTION IN CAENORHABDITIS-ELEGANS [J].
BLUMENTHAL, T .
TRENDS IN GENETICS, 1995, 11 (04) :132-136
[5]  
BRENNER S, 1974, GENETICS, V77, P71
[6]   The capsaicin receptor: a heat-activated ion channel in the pain pathway [J].
Caterina, MJ ;
Schumacher, MA ;
Tominaga, M ;
Rosen, TA ;
Levine, JD ;
Julius, D .
NATURE, 1997, 389 (6653) :816-824
[7]   A capsaicin-receptor homologue with a high threshold for noxious heat [J].
Caterina, MJ ;
Rosen, TA ;
Tominaga, M ;
Brake, AJ ;
Julius, D .
NATURE, 1999, 398 (6726) :436-441
[8]   MECHANISMS OF RHODOPSIN INACTIVATION IN-VIVO AS REVEALED BY A COOH-TERMINAL TRUNCATION MUTANT [J].
CHEN, J ;
MAKINO, CL ;
PEACHEY, NS ;
BAYLOR, DA ;
SIMON, MI .
SCIENCE, 1995, 267 (5196) :374-377
[9]   IDENTIFICATION OF CALCINEURIN AS A KEY SIGNALING ENZYME IN LYMPHOCYTE-T ACTIVATION [J].
CLIPSTONE, NA ;
CRABTREE, GR .
NATURE, 1992, 357 (6380) :695-697
[10]   A putative cyclic nucleotide-gated channel is required for sensory development and function in C-elegans [J].
Coburn, CM ;
Bargmann, CI .
NEURON, 1996, 17 (04) :695-706