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

Rubeis, Silvia De; Pasciuto, Emanuela; Li, Ka Wan; Fernández, Esperanza; Marino, Daniele Di; Buzzi, A.; Ostroff, Linnaea E.; Klann, Eric; Zwartkruis, Fried; Komiyama, Noboru H.; Grant, Seth G. N.; Poujol, Christel; Choquet, Daniel; Achsel, Tilmann; Posthuma, Daniëlle; Smit, August B.; Bagni, Claudia

doi:10.1016/j.neuron.2013.06.039

Cited by 265 publications

(356 citation statements)

References 80 publications

Supporting

Mentioning

339

Contrasting

Order By: Relevance

“…Cytoplasmic FMRP-interacting protein 1 (CYFIP1) engages in two distinct molecular complexes where it coordinates mRNA translation and actin cytoskeleton remodeling to ensure correct dendritic spine formation 47 . CYFIP1, also known as specific Rac1-activated (SRA1)…”

Section: Accepted Manuscriptmentioning

confidence: 99%

“…FMRP tethers specific mRNAs to CYFIP1, which then sequesters the capbinding protein eIF4E and mediates translational repression 55 ( Figure 1). Translation of target mRNAs, such as Arc/Arg3.1 which are important for synaptic structure and function 47 , is…”

Section: Accepted Manuscriptmentioning

confidence: 99%

“…The equilibrium of the two complexes is controlled by small GTPase Rac1, which alters the conformation of CYFIP1 47,48,53 . The heteropentameric WRC, consisting of the proteins WAVE1/2/3, ABI1/2, NCKAP1, HPSC300 and CYFIP1 or CYFIP2, is one of the critical modulators of actin filament reorganization in neurons 56 .…”

Section: Accepted Manuscriptmentioning

confidence: 99%

See 2 more Smart Citations

Dendritic spine actin cytoskeleton in autism spectrum disorder

Joensuu¹,

Lanoue

Hotulainen

2018

Progress in Neuro-Psychopharmacology and Biological Psychiatry

View full text Add to dashboard Cite

Section: Accepted Manuscriptmentioning

confidence: 99%

Section: Accepted Manuscriptmentioning

confidence: 99%

See 1 more Smart Citation

Dendritic spine actin cytoskeleton in autism spectrum disorder

Joensuu¹,

Lanoue

Hotulainen

2018

Progress in Neuro-Psychopharmacology and Biological Psychiatry

View full text Add to dashboard Cite

“…Gene expression, including protein synthesis, plays a well established role in neurotrophin-mediated neurite outgrowth (26,46,47,61,62). Moreover, inhibition of ribosomal biogenesis did not prevent activation of pro-dendritic signaling responses to BDNF but compromised translation regardless of the presence of BDNF.…”

Section: Table 4 Effects Of Shrnas On Bdnf-induced Dendrite Growthmentioning

confidence: 99%

Requirement of Neuronal Ribosome Synthesis for Growth and Maintenance of the Dendritic Tree

Słomnicki

Pietrzak

Vashishta

et al. 2016

Journal of Biological Chemistry

View full text Add to dashboard Cite

The nucleolus serves as a principal site of ribosome biogenesis but is also implicated in various non-ribosomal functions, including negative regulation of the pro-apoptotic transcription factor p53. Although disruption of the nucleolus may trigger the p53-dependent neuronal death, neurotoxic consequences of a selective impairment of ribosome production are unclear. Here, we report that in rat forebrain neuronal maturation is associated with a remarkable expansion of ribosomes despite postnatal down-regulation of ribosomal biogenesis. In cultured rat hippocampal neurons, inhibition of the latter process by knockdowns of ribosomal proteins S6, S14, or L4 reduced ribosome content without disrupting nucleolar integrity, cell survival, and signaling responses to the neurotrophin brain-derived neurotrophic factor. Moreover, reduced general protein synthesis and/or formation of RNA stress granules suggested diminished ribosome recruitment to at least some mRNAs. Such a translational insufficiency was accompanied by impairment of brain-derived neurotrophic factor-mediated dendritic growth. Finally, RNA stress granules and smaller dendritic trees were also observed when ribosomal proteins were depleted from neurons with established dendrites. Thus, a robust ribosomal apparatus is required to carry out protein synthesis that supports dendritic growth and maintenance. Consequently, deficits of ribosomal biogenesis may disturb neurodevelopment by reducing neuronal connectivity. Finally, as stress granule formation and dendritic loss occur early in neurodegenerative diseases, disrupted homeostasis of ribosomes may initiate and/or amplify neurodegeneration-associated disconnection of neuronal circuitries.The ribosome is the principal component of the protein synthesis machinery. Most steps of ribosomal biogenesis occur in the nucleolus starting with the RNA-polymerase-1 (pol 1) 2 -mediated transcription of rRNA genes (1). In addition, pol 1 activity is required for the maintenance of the nucleolus. Therefore, inhibition of pol 1 not only blocks ribosomal biogenesis but also perturbs non-ribosomal functions of the nucleolus, including negative regulation of the pro-apoptotic transcription factor p53 (2). Although pol 1 initiates ribosome production, many additional steps are required for that process, including rRNA processing and binding to ribosomal proteins (RPs) (3). Consequently, depletion of various RPs, including S6 or S14, disrupts ribosomal biogenesis without interfering with nucleolar integrity (4). Impaired ribosome production and/or ribosomal deficits are documented in various neurodegenerative diseases, including Alzheimer, Huntington, Parkinson, amyotrophic lateral sclerosis (ALS), and fronto-temporal lobe dementia (FTLD) (5-13). Reduced ribosomal biogenesis may also contribute to neurodevelopmental disorders. Thus, microcephaly and neurodevelopmental delays are present in Bowen-Conradi syndrome that is caused by deficiency of the ribosomal biogenesis factor EMG1 or in patients with a newly described RPL10 ribos...

show abstract

“…Synaptoneurosome Preparation-Synaptoneurosomes were prepared mainly as described in De Rubeis et al (15): cortices from young adult (P30 -P35) female mice (CD1) were homogenized in 1 ml of homogenization buffer (0.32 M sucrose, 0.1 mM CaCl 2 , 1 mM MgCl 2 , 0.1 mM PMSF) in ice using a Teflon glass homogenizer. The homogenate was brought to a final sucrose concentration of 1.25 M by adding 4.66 ml of 2 M sucrose and 2 ml of 0.1 mM CaCl 2 solution where after the sample was loaded into the centrifuge tubes and overlaid first with an equal volume of 1.0 M sucrose, 0.1 mM CaCl 2 solution and thereafter with the homogenization buffer.…”

Section: Methodsmentioning

confidence: 99%

Synaptic Synthesis, Dephosphorylation, and Degradation

Montanara

Rusconi

Locarno

et al. 2015

Journal of Biological Chemistry

View full text Add to dashboard Cite

Background: Although associated with intellectual disability, CDKL5 functions and regulation are poorly understood. Results: Upon neuronal activation, CDKL5 is dynamically regulated through local synthesis, dephosphorylation, and degradation. Conclusion: Neuronal activity and maturation control CDKL5 phosphorylation state and expression. Significance: This is the first report showing the activity-dependent modulation of CDKL5 in the neuronal periphery, further linking it to synapse development and plasticity.

show abstract

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

Cited by 265 publications

References 80 publications

Dendritic spine actin cytoskeleton in autism spectrum disorder

Dendritic spine actin cytoskeleton in autism spectrum disorder

Requirement of Neuronal Ribosome Synthesis for Growth and Maintenance of the Dendritic Tree

Synaptic Synthesis, Dephosphorylation, and Degradation

Contact Info

Product

Resources

About