Ephrin-B1 and ephrin-B2 mediate EphB-dependent presynaptic development via syntenin-1

Andrew C McClelland1, Sean I Sheffler-Collins, Matthew S Kayser

  • 1Department of Neuroscience, University of Pennsylvania School of Medicine, 1114 BRBII/III, 421 Curie Boulevard, Philadelphia, PA 19104, USA.

Insights

Ephrin-B1 and Ephrin-B2 are crucial for presynaptic development, working with EphB and syntenin-1 to form synapses. Their coordinated action ensures proper presynaptic specialization in the central nervous system.

Area of Science:

  • Neuroscience
  • Cell Biology
  • Molecular Biology

Background:

  • Synapse development requires presynaptic and postsynaptic coordination.
  • EphB receptors regulate postsynaptic development but their role in presynaptic formation is unclear.

Purpose of the Study:

  • To investigate the role of ephrin-B ligands and syntenin-1 in EphB-mediated presynaptic development.

Main Methods:

  • Knockdown of ephrin-B1, ephrin-B2, ephrin-B3, and syntenin-1 in presynaptic components.
  • Analysis of synaptic marker colocalization and synaptic specialization formation.

Main Results:

  • Knockdown of ephrin-B1, ephrin-B2, or syntenin-1 impaired EphB-dependent presynaptic development.
  • Ephrin-B1, ephrin-B2, and syntenin-1 form presynaptic clusters.
  • Ephrin-B1 and ephrin-B2 act independently in synapse formation but cooperatively recruit syntenin-1.

Conclusions:

  • Ephrin-B1 and ephrin-B2, along with syntenin-1, are essential mediators of presynaptic development in conjunction with EphB signaling.

Related Concept Videos

Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal01:22

Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal

Erythropoietin-producing hepatocellular carcinoma receptor (Eph) and its ligand, Eph receptor-interacting protein (Ephrin) were first discovered in the human carcinoma cell line, hence the name. Ephrin-Eph interaction guides cells to reach their appropriate location in adult tissues. They also play an essential role in the immune system by helping in immune cell migration, adhesion, and activation. Based on their structure and function, Eph is divided into two classes — EphA and EphB.
Integration of Synaptic Events01:28

Integration of Synaptic Events

Synaptic integration mainly includes the summation of graded potentials. Graded potentials, regardless of their type, cause subtle alterations in membrane voltage, resulting in either depolarization or hyperpolarization. These incremental changes, when combined or summed, can propel the neuron toward its threshold. Consider, for example, a membrane experiencing a +15 mV shift, causing it to depolarize from -70 mV to -55 mV. In this scenario, graded potentials govern the membrane's ability to...
Anchoring Junctions01:03

Anchoring Junctions

Anchoring junctions are multiprotein complexes that help cells connect to other cells and the extracellular matrix. Anchoring junctions are present on the lateral and basal surfaces of cells, providing strong and flexible connections. Focal adhesions are often formed due to cell interactions with the ECM substrata, which initiate signal transduction via kinase cascades and other mechanisms. Together, they provide stability and tissue integrity. There are three types of anchoring junctions:...
Fusion of Secretory Vesicles with the Plasma Membrane01:26

Fusion of Secretory Vesicles with the Plasma Membrane

Proteins and neurotransmitters in secretory vesicles can be released from a cell upon vesicle docking, priming, and fusion with the plasma membrane. Vesicles are docked and primed in preparation for the quick exocytosis of their contents in response to a stimulus. The fusion process is mainly carried out by a SNAP Receptor or SNARE complex, consisting of synaptobrevin, syntaxin-1, and SNAP-25.
In 1993, Jim Rothman proposed that the antiparallel pairing of vesicular and transmembrane SNAREs, or...
Catenins01:23

Catenins

Catenins are characterized by multiple binding domains and dynamic structures that allow them to function as linker proteins in cell junction complexes. All catenins, except α-catenin, contain a characteristic protein sequence called the armadillo repeat and are therefore also called armadillo proteins.
Catenins in Cell Junctions
Catenins bind to cell adhesion molecules such as cadherins and link them to different cytoskeletal proteins depending on the type of cell junction. At the adherens...
Chemical Synapses01:26

Chemical Synapses

Chemical synapses are specialized sites between two neurons or between a neuron and a non-neuronal cell like a muscle, glandular or sensory cell.
Because chemical synapses depend on the release of neurotransmitter molecules from synaptic vesicles to pass on their signal, there is an approximately one millisecond delay between when the axon potential reaches the presynaptic terminal and when the neurotransmitter leads to opening of postsynaptic ion channels. Additionally, this signaling is...