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Related Concept Videos

The Synapse02:47

The Synapse

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Neurons communicate with one another by passing on their electrical signals to other neurons. A synapse is the location where two neurons meet to exchange signals. At the synapse, the neuron that sends the signal is called the presynaptic cell, while the neuron that receives the message is called the postsynaptic cell. Note that most neurons can be both presynaptic and postsynaptic, as they both transmit and receive information.
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Tissue-specific transcription factors contribute to diverse cellular functions in mammals. For example, the gene for beta globin, a major component of hemoglobin, is present in all cells of the body. However, it is only expressed in red blood cells because the transcription factors that can bind to the promoter sequences of the beta globin gene are only expressed in these cells. Tissue-specific transcription factors also ensure that mutations in these factors may impair only the function of...
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For transition metal complexes, the coordination number determines the geometry around the central metal ion. Table 1 compares coordination numbers to molecular geometry. The most common structures of the complexes in coordination compounds are octahedral, tetrahedral, and square planar.
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In most main group element compounds, the valence electrons of the isolated atoms combine to form chemical bonds that satisfy the octet rule. For instance, the four valence electrons of carbon overlap with electrons from four hydrogen atoms to form CH4. The one valence electron leaves sodium and adds to the seven valence electrons of chlorine to form the ionic formula unit NaCl (Figure 1a). Transition metals do not normally bond in this fashion. They primarily form coordinate covalent bonds, a...
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Transcription01:10

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Overview
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Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a  complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
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Environmental Modulations of the Number of Midbrain Dopamine Neurons in Adult Mice
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The THO Complex Coordinates Transcripts for Synapse Development and Dopamine Neuron Survival.

Celine I Maeder1, Jae-Ick Kim2, Xing Liang1

  • 1Department of Biology, Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305, USA.

Cell
|August 28, 2018
PubMed
Summary
This summary is machine-generated.

The THO nuclear export complex (THOC) regulates synaptic protein synthesis and synapse development. Disrupting THOC impairs mRNA export, leading to neuronal defects and loss of dopamine function in C. elegans and mice.

Keywords:
CREBTHO complexcoordinated genetic programdopamine neuronsneurodegenerationnuclear exportpresynapse assembly

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Area of Science:

  • Neuroscience
  • Molecular Biology
  • Genetics

Background:

  • Synaptogenesis requires coordinated synthesis of synaptic vesicle and active zone proteins.
  • Molecular mechanisms governing the synthesis of these proteins remain poorly understood.

Purpose of the Study:

  • To identify molecular regulators of presynapse development.
  • To elucidate the role of nuclear export in neuronal function and survival.

Main Methods:

  • Forward genetic screens in C. elegans.
  • Analysis of THO nuclear export complex (THOC) mutants.
  • Investigated CRE binding protein (CREB) interaction with THOC.
  • Utilized mouse models of dopaminergic neuron dysfunction.

Main Results:

  • THOC complex identified as crucial for presynapse development in C. elegans dopaminergic neurons.
  • THOC mutants exhibit nuclear retention of synaptic mRNAs, decreased synaptic protein expression, and synapse loss.
  • CREB interacts with THOC to facilitate nuclear export of synaptic transcripts.
  • Thoc5 deletion in mouse dopaminergic neurons leads to synapse maintenance defects, neuronal death, and motor deficits.

Conclusions:

  • Nuclear export mechanisms are critical for regulating specific mRNA export and protein synthesis in neurons.
  • THOC acts as a rate-limiting factor in neuronal differentiation and survival by controlling synaptic mRNA export.