RNA-binding protein Sam68 controls synapse number and local β-actin mRNA metabolism in dendrites

@article{Klein2013RNAbindingPS,
  title={RNA-binding protein Sam68 controls synapse number and local $\beta$-actin mRNA metabolism in dendrites},
  author={Matthew E. Klein and Thomas J. Younts and Pablo E. Castillo and Bryen A Jordan},
  journal={Proceedings of the National Academy of Sciences},
  year={2013},
  volume={110},
  pages={3125 - 3130}
}
Proper synaptic function requires the spatial and temporal compartmentalization of RNA metabolism via transacting RNA-binding proteins (RBPs). Loss of RBP activity leads to abnormal posttranscriptional regulation and results in diverse neurological disorders with underlying deficits in synaptic morphology and transmission. Functional loss of the 68-kDa RBP Src associated in mitosis (Sam68) is associated with the pathogenesis of the neurological disorder fragile X tremor/ataxia syndrome. Sam68… 

Figures from this paper

Proteostasis and RNA Binding Proteins in Synaptic Plasticity and in the Pathogenesis of Neuropsychiatric Disorders

TLDR
Recent scientific findings are summarized, ongoing questions are highlighted, and basic molecular mechanisms to the pathogenesis of common neuropsychiatric disorders are linked.

Unraveling the Pathways to Neuronal Homeostasis and Disease: Mechanistic Insights into the Role of RNA-Binding Proteins and Associated Factors

TLDR
This review discusses the roles of Pumilio, Staufen, IGF2BP, FMRP, Sam68, CPEB, NOVA, ELAVL, SMN, TDP43, FUS, TAF15, and TIA1/TIAR in RNA metabolism by analyzing their specific molecular and cellular function, the neurological symptoms associated with their perturbation, and their axodendritic transport/localization.

Single β-Actin mRNA Detection in Neurons Reveals a Mechanism for Regulating Its Translatability

TLDR
This work uses single-molecule in situ hybridization to demonstrate that dendritic β-actin messenger RNA (mRNA) and ribosomes are in a masked, neuron-specific form and transient alteration of mRNA availability during synaptic plasticity is revealed.

Regulation of Neuronal Excitability by the RNA-Binding Protein Rbfox1

TLDR
The regulation of interneuron-specific Vamp1 by Rbfox1 provides a paradigm for broadly expressed RNA- binding proteins performing specialized functions in defined neuronal subtypes.

A Sam68‐dependent alternative splicing program shapes postsynaptic protein complexes

TLDR
It is found that Sam68 is required for the regulation of a set of alternative splicing events in pre‐mRNAs encoding several postsynaptic scaffolding molecules that are central to the function of GABAergic and glutamatergic synapses.

Control of a neuronal morphology program by an RNA-binding zinc finger protein, Unkempt.

TLDR
A molecular program that controls the early morphology of neurons through a metazoan-specific zinc finger protein, Unkempt, is described and its precise binding sites within coding regions of mRNAs linked to protein metabolism and trafficking are identified.

β-Actin mRNA interactome mapping by proximity biotinylation

TLDR
This work developed a RNA proximity biotinylation technique by tethering biotin ligase via MS2 coat protein at the 3′ UTR of endogenous MS2-tagged β-actin mRNA in mouse embryonic fibroblasts that allows the identification of functionally important proteins required for mRNA localization.
...

References

SHOWING 1-10 OF 46 REFERENCES

RNA Binding Proteins Accumulate at the Postsynaptic Density with Synaptic Activity

TLDR
The results suggest that hnRNP proteins regulate dendritic spine density and may play a role in synaptodendritic mRNA metabolism.

Zipcode Binding Protein 1 Regulates the Development of Dendritic Arbors in Hippocampal Neurons

TLDR
It was shown that proper cellular levels of ZBP1, its ability to engage in mRNA binding, and Src-dependent release of mRNA cargo from ZBP 1 are vital for dendritic arbor development in cultured rat hippocampal neurons and that β-actin overexpression significantly alleviated the effects of Z BP1 knockdown.

Specific interaction between Sam68 and neuronal mRNAs: Implication for the activity‐dependent biosynthesis of elongation factor eEF1A

TLDR
In cultured hippocampal neurons and in adult brain, the splicing regulatory protein Sam68 is partially relocated to the somatodendritic domain and associates with dendritic polysomes, and the proposal that endogenous Sam68 may contribute to the translational efficiency of the Eef1a1 mRNA is supported.

The nuclear RNA-binding protein Sam68 translocates to the cytoplasm and associates with the polysomes in mouse spermatocytes.

TLDR
It is demonstrated that Sam68 shuttles between the nucleus and the cytoplasm in secondary spermatocytes, suggesting that it may promote translation of specific RNA targets during the meiotic divisions.

Sam68 Regulates a Set of Alternatively Spliced Exons during Neurogenesis

TLDR
Using RNA interference knockdown of Sam68 expression and splicing-sensitive microarrays, a set of alternative exons whose splicing depends on Sam68 are identified and detailed analysis of one newly identified target exon in epsilon sarcoglycan (Sgce) showed that both RNA elements distributed across the adjacent introns and the RNA binding activity of Sam 68 are necessary to repress the Sgce exon.

Identification of cellular mRNA targets for RNA-binding protein Sam68.

TLDR
Results indicated that Sam68 recognizes both the UAAA motif and poly(U) sequences in vivo for binding to cellular target mRNAs.

Activity-Dependent Trafficking and Dynamic Localization of Zipcode Binding Protein 1 and β-Actin mRNA in Dendrites and Spines of Hippocampal Neurons

TLDR
The activity-dependent trafficking of ZBP1 and its dynamic movements within dendritic spines provide new evidence to implicate RNA binding proteins as regulators of mRNA transport to activated synapses in response to synaptic activity.

Limited availability of ZBP1 restricts axonal mRNA localization and nerve regeneration capacity

TLDR
A direct role for ZBP1 in transport and translation of mRNA cargos in axonal regeneration in vitro and in vivo is supported.

Spatial regulation of β-actin translation by Src-dependent phosphorylation of ZBP1

TLDR
It is shown that chicken ZBP1 modulates the translation of β-actin mRNA, which is important for cell migration and neurite outgrowth.