Gap junctions and connexins: potential contributors to the immunological synapse

Ernesto Oviedo-Orta1, W Howard Evans

  • 1Bristol Heart Institute, Bristol Royal Infirmary, United Kingdom. e.oviedo-orta@bristol.ac.uk

Insights

Lymphocytes utilize connexins (protein building blocks of gap junctions) for intercellular communication. These connexins influence immune responses by regulating the release of signaling molecules, impacting lymphocyte function.

Area of Science:

  • Immunology
  • Cell Biology
  • Biochemistry

Background:

  • Gap junctional communication facilitates metabolic coupling between adjacent cells.
  • Lymphocytes express connexins, the protein components of gap junctions, including connexin 40 and connexin 43.
  • Connexins are implicated in lymphocyte physiology, influencing immunoglobulin and cytokine secretion.

Purpose of the Study:

  • To investigate the role of connexins and gap junctional communication in lymphocyte function.
  • To explore the potential paracrine functions of lymphocyte connexins beyond traditional gap junctions.
  • To understand the contribution of lymphocyte gap junctional communication to the immunological synapse.

Main Methods:

  • Utilized connexin mimetic peptides to inhibit gap junctional communication in T and B lymphocyte cocultures.
  • Analyzed the effects of inhibition on immunoglobulin and cytokine secretion.
  • Examined the potential involvement of gap junction hemichannels in metabolite release.

Main Results:

  • Inhibitors of gap junctional communication reduced immunoglobulin and cytokine secretion by lymphocytes.
  • Evidence suggests connexins may have paracrine functions through hemichannel activity, releasing molecules like ATP.
  • Connexins are increasingly recognized for their role in lymphocyte signaling.

Conclusions:

  • Connexins play a fundamental role in lymphocyte physiology and immune responses.
  • Lymphocyte connexins may function not only in gap junctions but also via hemichannels, mediating paracrine signaling.
  • Gap junctional communication is a significant component of the complex signaling network within the immunological synapse.

Related Concept Videos

Contact-dependent Signaling01:19

Contact-dependent Signaling

Contact-dependent signaling, as the name suggests, requires that communicating cells be in direct contact with each other. This is achieved either through receptor-ligand interactions or by specialized cytoplasmic channels that allow the flow of small molecules between cells. In animal cells, channels called gap junctions facilitate contact-dependent signaling in certain tissues, whereas, plasmodesmata perform a similar function in plants.
Gap Junctions
In animal cells, gap junctions are formed...
Gap Junctions01:37

Gap Junctions

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...
Electrical Synapses01:28

Electrical Synapses

Electrical synapses found in all nervous systems play important and unique roles. In these synapses, the presynaptic and postsynaptic membranes are very close together (3.5 nm) and are actually physically connected by channel proteins forming gap junctions.
Gap junctions allow the current to pass directly from one cell to the next. In contrast, in the chemical synapse, the neurotransmitters carry the information through the synaptic cleft from one neuron to the next. They consist of two...
Overview of Cell-Cell Junctions01:14

Overview of Cell-Cell Junctions

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.
Occluding or Tight Junctions
Tight...
Gap Junctions01:27

Gap Junctions

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...
Overview of Cell-Cell Junctions01:14

Overview of Cell-Cell Junctions

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.
Occluding or Tight Junctions
Tight...