CYFIP1 Coordinates mRNA Translation and Cytoskeleton Remodeling to Ensure Proper Dendritic Spine Formation

被引：227

作者：

De Rubeis, Silvia ^{[1
,2
,3
]}

Pasciuto, Emanuela ^{[1
,2
,3
]}

Li, Ka Wan ^{[4
]}

Fernandez, Esperanza ^{[1
,2
,3
]}

Di Marino, Daniele ^{[1
,2
,3
]}

Buzzi, Andrea ^{[1
,2
,3
]}

Ostroff, Linnaea E. ^{[7
]}

Klann, Eric ^{[7
]}

Zwartkruis, Fried J. T. ^{[8
,9
]}

Komiyama, Noboru H. ^{[10
,11
]}

Grant, Seth G. N. ^{[10
,11
]}

Poujol, Christel ^{[12
,13
]}

Choquet, Daniel ^{[14
,15
]}

Achsel, Tilmann ^{[1
,2
,3
]}

Posthuma, Danielle ^{[5
,6
,16
]}

Smit, August B. ^{[4
]}

Bagni, Claudia ^{[1
,2
,3
,17
]}

机构：

[1] KULeuven, VIB Ctr Biol Dis, B-3000 Leuven, Belgium

[2] KULeuven, Ctr Human Genet, B-3000 Leuven, Belgium

[3] KULeuven, LIND, B-3000 Leuven, Belgium

[4] VU Univ Med Ctr Amsterdam, Ctr Neurogen & Cognit Res, Dept Mol & Cellular Neurobiol, NL-1081 HV Amsterdam, Netherlands

[5] VU Univ Med Ctr Amsterdam, Ctr Neurogen & Cognit Res, Dept Funct Genom, NL-1081 HV Amsterdam, Netherlands

[6] VU Univ Med Ctr Amsterdam, Ctr Neurogen & Cognit Res, Dept Clin Genet, NL-1081 HV Amsterdam, Netherlands

[7] NYU, Ctr Neural Sci, New York, NY 10003 USA

[8] Univ Med Ctr Utrecht, Ctr Biomed Genet, NL-3584 CG Utrecht, Netherlands

[9] Univ Med Ctr Utrecht, Canc Genom Ctr, NL-3584 CG Utrecht, Netherlands

[10] Univ Edinburgh, Ctr Clin Brain Sci, Edinburgh EH16 4SB, Midlothian, Scotland

[11] Univ Edinburgh, Ctr Neuroregenerat, Edinburgh EH16 4SB, Midlothian, Scotland

[12] CNRS, Bordeaux Imaging Ctr, UMS 3420, F-33000 Bordeaux, France

[13] Univ Bordeaux, UMS 3420, F-33077 Bordeaux, France

[14] CNRS, Interdisciplinary Inst Neurosci, IINS, UMR 5297, F-33000 Bordeaux, France

[15] Univ Bordeaux, UMR 5297, F-33077 Bordeaux, France

[16] Erasmus Univ, Sophia Child Hosp, Dept Child & Adolescent Psychiat, Med Ctr, NL-3000 CB Rotterdam, Netherlands

[17] Univ Roma Tor Vergata, Dept Biomed & Prevent, I-00133 Rome, Italy

来源：

NEURON | 2013年 / 79卷 / 06期

基金：

欧盟第七框架计划; 英国惠康基金;

关键词：

FRAGILE-X-SYNDROME; LOCAL PROTEIN-SYNTHESIS; SYNAPTIC PLASTICITY; MAMMALIAN TARGET; CRITICAL REGION; MOUSE MODEL; RAC1; FMRP; MECHANISMS; AUTISM;

D O I：

10.1016/j.neuron.2013.06.039

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

The CYFIP1/SRA1 gene is located in a chromosomal region linked to various neurological disorders, including intellectual disability, autism, and schizophrenia. CYFIP1 plays a dual role in two apparently unrelated processes, inhibiting local protein synthesis and favoring actin remodeling. Here, we show that brain-derived neurotrophic factor (BDNF)-driven synaptic signaling releases CYFIP1 from the translational inhibitory complex, triggering translation of target mRNAs and shifting CYFIP1 into the WAVE regulatory complex. Active Rac1 alters the CYFIP1 conformation, as demonstrated by intramolecular FRET, and is key in changing the equilibrium of the two complexes. CYFIP1 thus orchestrates the two molecular cascades, protein translation and actin polymerization, each of which is necessary for correct spine morphology in neurons. The CYFIP1 interactome reveals many interactors associated with brain disorders, opening new perspectives to define regulatory pathways shared by neurological disabilities characterized by spine dysmorphogenesis.

引用

页码：1169 / 1182

页数：14

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