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Related Concept Videos

Cotranslational Protein Translocation01:20

Cotranslational Protein Translocation

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Translocation of proteins across membranes is an ancient process that occurs even in bacteria and archaebacteria. In fact, the components of the translocation machinery are still conserved between prokaryotes and eukaryotes.
Sec61 channel partners for cotranslational translocation
During cotranslational translocation, the Sec61 channel partners with the signal recognition particle (SRP), the signal recognition particle receptor (SR), and the ribosomes to transport the nascent polypeptide chain...
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Leaky Scanning02:28

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During most eukaryotic translation processes, the small 40S ribosome subunit scans an mRNA from its 5' end until it encounters the first start AUG codon. The large 60S ribosomal subunit then joins the smaller one to initiate protein synthesis. The location of the translation initiation is largely determined by the nucleotides near the start codon as there may be multiple translation initiation sites present on the mRNA.  Marilyn Kozak discovered that the sequence RCCAUGG (where R...
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Post-translational Translocation of Proteins to the RER01:27

Post-translational Translocation of Proteins to the RER

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A sizable fraction of proteins destined for ER are first synthesized in the cell cytosol and then transported across the ER membrane–a process called post-translational translocation. Similar to cotranslationally translocated proteins, these proteins also use the Sec translocon complex to enter the ER lumen.
Targeting proteins to the ER
Hsp40 and Hsp70 chaperone molecules bind the translated proteins in the cytosol to prevent their folding. The chaperone binding helps to keep the signal...
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Directing Proteins to the Rough Endoplasmic Reticulum01:34

Directing Proteins to the Rough Endoplasmic Reticulum

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The organelle-specific signaling sequences direct proteins synthesized in the cytosol to their final destination like ER, mitochondria, peroxisomes, etc. Some of the proteins directed to ER are then trafficked via vesicles to other organelles within the cell or the extracellular environment through the Golgi complex. For example, the rough ER synthesizes soluble proteins for transportation to the lysosomes or secretion out of the cell. It can also synthesize transmembrane proteins that can...
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Regulated mRNA Transport02:22

Regulated mRNA Transport

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In eukaryotes, transcription and translation are compartmentalized; an mRNA is first synthesized in the nucleus and then selectively transported to the cytoplasm for protein synthesis. Before transport, a pre-mRNA undergoes several steps of post-transcriptional modifications including splicing, 5' capping, and the addition of a poly-adenine tail. Various proteins bind to the pre-mRNA during these modifications. The mRNA transport takes place with the help of multiple proteins playing...
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Isolation and Quantification of Axonal mRNAs Using Porous Membrane Inserts and RTddPCR
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Isolation and Quantification of Axonal mRNAs Using Porous Membrane Inserts and RTddPCR

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Axonal cap-dependent translation regulates presynaptic p35.

Kuangfu Hsiao1, Ozlem Bozdagi, Deanna L Benson

  • 1Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine and Graduate School of Biomedical Sciences at Mount Sinai, New York, New York, 10029.

Developmental Neurobiology
|November 21, 2013
PubMed
Summary
This summary is machine-generated.

Intra-axonal protein synthesis, specifically of p35, is crucial for regulating synaptic vesicle recycling pools in developing neurons. Targeted translational repression offers a new method to study this process.

Keywords:
Cdk5cap-dependent translationmRNA transporttargeted repressionvesicle recycling

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Area of Science:

  • Neuroscience
  • Molecular Biology
  • Cell Biology

Background:

  • Axonal growth cones and axons translate proteins locally for development and injury response.
  • Intra-axonal translation contributes to synapse formation, but its role is not well understood.
  • Local protein synthesis impacts neuronal plasticity and function.

Purpose of the Study:

  • To investigate the role of intra-axonal cap-dependent protein translation in developing central nervous system (CNS) synapses.
  • To understand the presynaptic contributions of local protein synthesis to synaptic development.
  • To explore the function of extrasomal protein synthesis in neurons.

Main Methods:

  • Engineered a subcellular-targeting translational repressor to inhibit axonal mRNA translation.
  • Utilized this strategy to study cap-dependent protein translation in developing CNS synapses.
  • Quantified synaptic vesicle recycling pool size and p35 protein levels.

Main Results:

  • Intra-axonal mRNA translation restrains synaptic vesicle recycling pool size.
  • p35, a Cdk5 activating protein, was identified as a target of this regulation.
  • Repressing translation reduced p35 levels and vesicle recycling pools; restoring p35 rescued these pools.

Conclusions:

  • Intra-axonal synthesis of p35 is essential for normal vesicle recycling in developing neurons.
  • Targeted translational repression is a novel strategy for investigating extrasomal protein synthesis.
  • Local protein synthesis plays a critical role in synaptic development and function.