Silencing of Odorant Receptor Genes by G Protein βγ Signaling Ensures the Expression of One Odorant Receptor per Olfactory Sensory Neuron

被引：39

作者：

Ferreira, Todd ^{[1
,2
]}

Wilson, Sarah R. ^{[1
,2
]}

Choi, Yoon Gi ^{[3
]}

Risso, Davide ^{[5
]}

Dudoit, Sandrine ^{[4
,5
]}

Speed, Terence P. ^{[5
,6
]}

Ngai, John ^{[1
,2
,3
]}

机构：

[1] Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA

[2] Univ Calif Berkeley, Helen Wills Neurosci Inst, Berkeley, CA 94720 USA

[3] Univ Calif Berkeley, Funct Genom Lab, Berkeley, CA 94720 USA

[4] Univ Calif Berkeley, Div Biostat, Berkeley, CA 94720 USA

[5] Univ Calif Berkeley, Dept Stat, Berkeley, CA 94720 USA

[6] Royal Melbourne Hosp, Walter & Eliza Hall Inst Med Res, Bioinformat Div, Parkville, Vic 3050, Australia

来源：

NEURON | 2014年 / 81卷 / 04期

基金：

美国国家科学基金会;

关键词：

MOUSE; SYSTEM; MAP; FEEDBACK; METHYLTRANSFERASE; ORGANIZATION; INFORMATION; ACTIVATION; G-GAMMA-13; SEQUENCES;

D O I：

10.1016/j.neuron.2014.01.001

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Olfactory sensory neurons express just one out of a possible similar to 1,000 odorant receptor genes, reflecting an exquisite mode of gene regulation. In one model, once an odorant receptor is chosen for expression, other receptor genes are suppressed by a negative feedback mechanism, ensuring a stable functional identity of the sensory neuron for the lifetime of the cell. The signal transduction mechanism subserving odorant receptor gene silencing remains obscure, however. Here, we demonstrate in the zebrafish that odorant receptor gene silencing is dependent on receptor activity. Moreover, we show that signaling through G protein beta gamma subunits is both necessary and sufficient to suppress the expression of odorant receptor genes and likely acts through histone methylation to maintain the silenced odorant receptor genes in transcriptionally inactive heterochromatin. These results link receptor activity with the epigenetic mechanisms responsible for ensuring the expression of one odorant receptor per olfactory sensory neuron.

引用

页码：847 / 859

页数：13

共 56 条

[11] RACK1 regulates specific functions of Gβγ [J].

Chen, SH ;

Dell, EJ ;

Lin, F ;

Sai, JQ ;

Hamm, HE .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2004, 279 (17) :17861-17868

[12] RACK1 regulates directional cell migration by acting on Gβγ at the interface with its effectors PLCβ and PI3Kγ [J].

Chen, Songhai ;

Lin, Fang ;

Shin, Myung Eun ;

Wang, Fei ;

Shen, Lixin ;

Hamm, Heidi E. .

MOLECULAR BIOLOGY OF THE CELL, 2008, 19 (09) :3909-3922

[13] ALLELIC INACTIVATION REGULATES OLFACTORY RECEPTOR GENE-EXPRESSION [J].

CHESS, A ;

SIMON, I ;

CEDAR, H ;

AXEL, R .

CELL, 1994, 78 (05) :823-834

[14] Nuclear Aggregation of Olfactory Receptor Genes Governs Their Monogenic Expression [J].

Clowney, E. Josephine ;

LeGros, Mark A. ;

Mosley, Colleen P. ;

Clowney, Fiona G. ;

Markenskoff-Papadimitriou, Eirene C. ;

Myllys, Markko ;

Barnea, Gilad ;

Larabell, Carolyn A. ;

Lomvardas, Stavros .

CELL, 2012, 151 (04) :724-737

[15] Co-Opting the Unfolded Protein Response to Elicit Olfactory Receptor Feedback [J].

Dalton, Ryan P. ;

Lyons, David B. ;

Lomvardas, Stavros .

CELL, 2013, 155 (02) :321-332

[16] Filtering of Visual Information in the Tectum by an Identified Neural Circuit [J].

Del Bene, Filippo ;

Wyart, Claire ;

Robles, Estuardo ;

Tran, Amanda ;

Looger, Loren ;

Scott, Ethan K. ;

Isacoff, Ehud Y. ;

Baier, Herwig .

SCIENCE, 2010, 330 (6004) :669-673

[17] The cell biology of smell [J].

DeMaria, Shannon ;

Ngai, John .

JOURNAL OF CELL BIOLOGY, 2010, 191 (03) :443-452

[18] The Role of Gβγ Subunits in the Organization, Assembly, and Function of GPCR Signaling Complexes [J].

Dupre, Denis J. ;

Robitaille, Melanie ;

Rebois, R. Victor ;

Hebert, Terence E. .

ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY, 2009, 49 :31-56

[19] IDENTIFICATION OF 2 FAMILIES OF SATELLITE-LIKE REPETITIVE DNA-SEQUENCES FROM THE ZEBRAFISH (BRACHYDANIO-RERIO) [J].

EKKER, M ;

FRITZ, A ;

WESTERFIELD, M .

GENOMICS, 1992, 13 (04) :1169-1173

[20]

FAURE M, 1994, J BIOL CHEM, V269, P7851

← 1 2 3 4 5 6 →