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Related Concept Videos

Gap Junctions01:37

Gap Junctions

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Multicellular organisms employ a variety of ways for cells to communicate with each other. Gap junctions are specialized proteins that form pores between neighboring cells in animals, connecting the cytoplasm between the two, and allowing for the exchange of molecules and ions. They are found in a wide range of invertebrate and vertebrate species, mediate numerous functions including cell differentiation and development, and are associated with numerous human diseases, including cardiac and...
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Gap Junctions01:27

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The cytoplasm of adjacent animal cells can exchange small molecules, ions, and secondary messengers via the communication channels which form the gap junctions. These junctions comprise a few hundred to thousands of molecular channels, each made of two halves, called the connexon hemichannel. A connexon is a hexamer of six transmembrane connexin proteins, which assemble radially, thus forming a pore or channel in the center. One connexon hemichannel docks with a corresponding connexon on the...
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Conventional electron microscopy (EM) involves dehydration, fixation, and staining of biological samples, which distorts the native state of biological molecules and results in several artifacts. Also, the high-energy electron beam damages the sample and makes it difficult to obtain high-resolution images. These issues can be addressed using cryo-EM, which uses frozen samples and gentler electron beams. The technique was developed by Jacques Dubochet, Joachim Frank, and Richard Henderson, for...
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Mechanically-gated Ion Channels01:12

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Mechanically-gated ion channels are proteins found in eukaryotic and prokaryotic cell membranes that open in response to mechanical stress. Tension, compression, swelling, and shear stress can alter the conformation of the protein, opening a transmembrane channel that allows the passage of ions for signal transmission. In eukaryotes, mechanically-gated channels are distributed in several regions like the neurons, lungs, skin, bladder, and heart, where they play critical roles in numerous...
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Non-gated Ion Channels01:24

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Ion channels are specialized proteins on the plasma membrane that allow charged ions to pass down their electrochemical gradient. Their main function is to maintain the membrane potential which is critical for cell viability. These channels are either gated or non-gated and can transport more than a thousand ions within milliseconds for the cellular event to occur.
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The complex three-dimensional arrangement of cells in any multicellular organism is defined and maintained by interactions of cells with each other and the extracellular matrix. Cell-cell junctions are specialized structures where the multi-protein complexes on one cell interact with the multi-protein complexes on another  cell. These cell junctions are classified  into three main types based on their function — occluding, anchoring, and gap junctions.
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Structural insights into gap junction channels boosted by cryo-EM.

Atsunori Oshima1

  • 1Cellular and Structural Physiology Institute (CeSPI), Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601, Japan; Department of Basic Medicinal Sciences, Graduate School of Pharmaceutical Sciences, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601, Japan.

Current Opinion in Structural Biology
|April 28, 2020
PubMed
Summary

Understanding gap junction channels is key for cell communication. Recent cryo-electron microscopy (cryo-EM) studies reveal structural differences in lipids, aiding the understanding of channel regulation.

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Area of Science:

  • Structural biology
  • Cellular biology
  • Biophysics

Background:

  • Intercellular communication is vital for multicellular life.
  • Gap junction channels are crucial for this communication.
  • Molecular mechanisms of gap junction channel gating remain elusive.

Purpose of the Study:

  • To review recent cryo-electron microscopy (cryo-EM) studies on gap junction channel structures.
  • To highlight structural differences observed in lipidic environments versus detergent-solubilized states.
  • To provide insights into the regulatory mechanisms of gap junction channel function.

Main Methods:

  • Single-particle cryo-electron microscopy (cryo-EM) for high-resolution structure determination.
  • Analysis of gap junction channel structures in different membrane environments.
  • Comparison of structures in lipid bilayers versus detergent micelles.

Main Results:

  • Cryo-EM has enabled high-resolution visualization of challenging membrane proteins like gap junction channels.
  • Significant structural variations exist between gap junction channels in lipid bilayers and detergent-solubilized forms.
  • These structural differences offer clues to the channels' opening and closing mechanisms.

Conclusions:

  • Cryo-EM is instrumental in solving the structures of membrane proteins.
  • Lipid environments are critical for understanding the native structure and function of gap junction channels.
  • Structural insights from cryo-EM studies are advancing the understanding of gap junction channel regulation.