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Related Concept Videos

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Clathrin-coated vesicles use endocytosis to transport receptors and lysosomal hydrolases from the Golgi to the lysosome in the late secretory pathway. Clathrin-mediated endocytosis was the first described endocytic process, and Clathrin-coated vesicles remain one of the most well-studied transport vesicles. The molecular machinery that generates clathrin-coated vesicles comprises over 50 proteins that precisely coordinate vesicle formation. Cell surface receptors concentrated in indented sites...
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Complex microtubule structures are present in resting cells and in dividing cells. In resting cells, they are responsible for maintaining the cellular architecture, tracks for intracellular transport, positioning of organelles, assembly of cilia and flagella. They mediate the bipolar spindle assembly for chromosomal segregation and positioning of the cell division plate in dividing cells. The formation of microtubule complex structures depends on the cell type, cell stage, and cell function.
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Vesicle budding is orchestrated by distinct cytosolic proteins such as adaptor proteins, coat proteins, and GTPases. To initiate vesicle budding, membrane-bending proteins containing crescent-shaped BAR domains bind to the lipid heads in the bilayer and distort the membrane to form a protein-coated vesicle bud. Adaptors proteins such as AP2 for clathrin-coated vesicles can nucleate on the deformed membrane. Finally, coat proteins such as clathrin or COPI and COPII assemble into a coat forming...
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Vesicles incorporate different coat protein subunits in different cell locations, which changes the properties of the coat, such as the shape and geometry of the transport vesicles. Thus, vesicle coat proteins also play a significant role in cargo selection.
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Cell polarity is the asymmetric distribution of cellular and membrane components, making one side of the cell different from the other. This polarity is essential to many processes such as embryogenesis, axon migration, glucose transport across epithelial cells, and directional cell migration. A migrating cell responds to intracellular or extracellular signals via molecular cascades that reorganize the actin cytoskeleton to establish this polarity. In these cells, the Rho family proteins Cdc42,...
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The intrinsic polarity of cells can be primarily attributed to two factors- i) the asymmetric accumulation of mobile components such are regulatory molecules and subcellular components across the cell and ii) the orientation of polar cytoskeletal filaments that make up the cytoskeletal networks, specifically microfilaments, and microtubules arranged along the axis of polarity. Interactions between the cytoskeletal filaments are crucial for the establishment and maintenance of the polar nature...
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In vivo and in vitro Studies of Adaptor-clathrin Interaction
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Two Clathrin Adaptor Protein Complexes Instruct Axon-Dendrite Polarity.

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Distinct dileucine motifs control protein sorting to neuronal axons or dendrites. These motifs interact with adaptor protein complexes (APs), with AP-3 targeting axons and AP-1 targeting dendrites.

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Area of Science:

  • Neuroscience
  • Cell Biology
  • Molecular Biology

Background:

  • Neuronal polarization, essential for function, involves establishing distinct axons and dendrites.
  • Mechanisms for sorting and targeting proteins to these neuronal compartments remain largely unknown.

Purpose of the Study:

  • To identify molecular signals and protein complexes responsible for transmembrane protein targeting to axons versus dendrites.
  • To elucidate the roles of clathrin-associated adaptor protein complexes (APs) in neuronal protein sorting.

Main Methods:

  • Identification of dileucine motifs in transmembrane proteins.
  • Analysis of protein interactions with adaptor protein complexes (APs) in C. elegans.
  • Localization studies of AP-1 and AP-3 within the Golgi apparatus.

Main Results:

  • Distinct dileucine motifs were identified as necessary and sufficient for axonal or dendritic targeting.
  • Axonal targeting is mediated by AP-3, while dendritic targeting is mediated by AP-1.
  • The axonal dileucine motif exhibits higher binding affinity for AP-3 than for AP-1.

Conclusions:

  • AP-3 and AP-1 directly select transmembrane proteins via dileucine motifs for sorting.
  • These APs mediate targeting to distinct vesicle pools, directing proteins to either the axon or dendrite.
  • This mechanism provides insight into the molecular basis of neuronal polarity establishment.