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Related Concept Videos

Hedgehog Signaling Pathway02:33

Hedgehog Signaling Pathway

The Hedgehog gene (Hh) was first discovered due to its control of the growth of disorganized, hair-like bristles phenotype in Drosophila, much like hedgehog spines. Hh plays a crucial role in the development of organs and the maintenance of homeostasis in both invertebrates and vertebrates. However, while Drosophila has only one Hh protein, mammals have multiple functional Hedgehog proteins - Sonic (Shh), Desert (Dhh), and Indian Hedgehog (Ihh). All of these homologous proteins have adapted to...
Hedgehog Signaling Pathway02:33

Hedgehog Signaling Pathway

The Hedgehog gene (Hh) was first discovered due to its control of the growth of disorganized, hair-like bristles phenotype in Drosophila, much like hedgehog spines. Hh plays a crucial role in the development of organs and the maintenance of homeostasis in both invertebrates and vertebrates. However, while Drosophila has only one Hh protein, mammals have multiple functional Hedgehog proteins - Sonic (Shh), Desert (Dhh), and Indian Hedgehog (Ihh). All of these homologous proteins have adapted to...
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Clathrin Coated Vesicles

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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COP Coated Vesicles00:59

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Membrane-enclosed structures called vesicles transport proteins and lipids across the cell. The vesicles derive their cargo from the plasma membrane, Golgi, ER, or endosome. Coated vesicles are spherical, protein-coated carriers with a 50–100 nm diameter that mediate bidirectional transport between the ER and the Golgi. The distribution of proteins between the ER and Golgi complex is dynamic and is maintained by different coated vesicles. Their formation is driven by the assembly of different...
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Mitochondria are double-membrane organelles of the eukaryotes involved in cellular metabolism, signaling, ATP synthesis, and programmed cell death.  Each of these processes requires specific proteins and enzymes that must be correctly sorted to the right mitochondrial subcompartment for the proper functioning of the organelle.
Most of these mitochondrial proteins are encoded by the nucleus and imported to the mitochondria as unfolded or loosely folded precursors. Mitochondrial precursors...

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Analysis of Endocytic Uptake and Retrograde Transport to the Trans-Golgi Network Using Functionalized Nanobodies in Cultured Cells
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Barcoding Hedgehog for intracellular transport.

Thomas B Kornberg1

  • 1Cardiovascular Research Institute, University of California, San Francisco, CA 94158, USA. tkornberg@ucsf.edu

Science Signaling
|November 25, 2011
PubMed
Summary
This summary is machine-generated.

Hedgehog protein movement is key for organ development. Its lipidation, with palmitate and cholesterol, may regulate extracellular transport or intracellular trafficking for release.

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Area of Science:

  • Developmental Biology
  • Cell Signaling
  • Molecular Biology

Background:

  • Hedgehog proteins are crucial signaling molecules regulating organ development in vertebrates and invertebrates.
  • The precise mechanisms governing Hedgehog protein transport between cells remain largely unknown.
  • Lipid modifications, including palmitoylation and cholesterylation, have been identified on Hedgehog proteins.

Purpose of the Study:

  • To investigate the role of lipid modifications in Hedgehog protein trafficking and signaling.
  • To elucidate the mechanisms controlling Hedgehog protein movement from source to target cells.
  • To differentiate between proposed models of extracellular transport versus intracellular packaging.

Main Methods:

  • Characterization of N-terminal palmitoylation and C-terminal cholesterylation of Hedgehog.
  • Analysis of the impact of lipidation on protein secretion and extracellular diffusion.
  • Investigation of intracellular pathways potentially involved in Hedgehog transport and release.

Main Results:

  • Lipid modifications, specifically palmitate and cholesterol, are covalently attached to the Hedgehog protein.
  • These lipophilic modifications are hypothesized to regulate Hedgehog movement in the extracellular space.
  • An alternative model suggests C-terminal cholesterol targets Hedgehog to intracellular pathways for encapsulated release.

Conclusions:

  • Lipid modifications play a significant role in regulating Hedgehog protein function and localization.
  • Further research is needed to definitively determine whether Hedgehog moves extracellularly or via intracellular trafficking.
  • Understanding Hedgehog transport mechanisms is critical for deciphering developmental signaling pathways.