Eph Receptor Signaling in Spine Morphology

Fig.1 Structural features of ephrins and Ephs and the concept of bidirectional signaling. (Klein, 2009)

Introduction of Eph Receptor

In vertebrates there are ten EphA and six EphB receptors: EphA1-EphA10 and EphB1-EphB6. The extracellular part of Eph receptors includes the N-terminal ephrin-binding domain, a cysteine-rich region (containing an epidermal growth factor (EGF)-like motif), and two fibronectin type III repeats. It is separated by a membrane-spanning segment from the cytoplasmic part, which includes a juxta membrane segment, the tyrosine kinase domain, and the sterile α motif (SAM). However, the kinase domain of one receptor from each class (EphA10 and EphB6) lacks residues that are essential for catalytic activity, which indicates that these two receptors might not function by phosphorylating cytoplasmic target proteins. More Eph receptor and ephrin variants are generated by alternative splicing and their structures differ from the prototypical domain structure.

Introduction of Spine

Spines are small, actin-enriched dendritic protrusions that can be sites of excitatory input. The dynamic formation and retraction of spines are thought to be one of the features underlying synaptic plasticity and possibly long-term memory. The formation of spines is believed to be triggered by axon-dendrite contact, whereas maturation is controlled by neuronal activity and by astrocytes that enwrap spines and axon terminals.

Research and Conclusions of Eph Receptor Signaling in Spine Morphology

In the hippocampus, several Ephs have been localized to dendrites and spines, and the use of null mutant mice has highlighted a functionally redundant requirement of three EphB receptors (EphB1-3) in dendritic spine morphogenesis. Cortical neurons from animals lacking EphB1-3 also have fewer spines, and when a fusion protein of the postsynaptic marker PSD-95 and green fluorescent protein (PSD-95 GFP) was introduced, the resulting puncta were found primarily along dendritic shafts. Postnatal re-expression of EphB2 in single cells in slice cultures from animals lacking EphB1-3 is sufficient to rescue dendritic spine defects and PSD-95 GFP localization on spine-like protrusions. EphB2 controls the formation of postsynaptic specializations acutely and cell-autonomously.

In cultured hippocampal neurons, EphB receptors regulate spine morphology by modulating the activity of Rho family GTPases. This may involve a protein complex that includes focal adhesion kinase (FAK), Src and paxillin, and ultimately leads to the activation of RhoA12. In contrast with EphAs, EphB2 interacts and cooperates with NMDA receptors (NMDARs) in synapse formation and plasticity.

Fig.2 Eph forward signaling modulates spine and synapse formation. (Klein, 2009)

Using time-lapse imaging of dissociated neurons and cortical slices, the same group found that loss of EphBs reduced the motility of postsynaptic dendritic filopodia (even though mutant filopodia were longer than EphB-expressing filopodia). Filopodial motility and synapse formation require EphB forward signaling that leads to activation of PAK, a serine/threonine kinase that regulates actin dynamics. Hence, EphB-mediated PAK activation may enhance the short-range filopodial exploration for synaptic partners. Notably, filopodial motility alone was not sufficient to drive synapse formation in this preparation. Instead, EphB signaling in filopodia had to be combined with trans-synaptic interaction with axonal ephrinBs to stabilize contacts and to induce synapse differentiation and spine morphogenesis.

Creative Biolabs has been focusing on neuro-based research over years. With years of experience accumulated from practice, we have established a comprehensive neuro-based technology platform providing a variety of relevant products and services to our customers. It is our strong foundations and rich experience that make us confident in offering top-rated customer experience to our clients.

If you are interested in neuro-based researches and need assistant, or you have any other questions about our services, please feel free to contact us for more information.

Reference

1. Klein, R. Bidirectional modulation of synaptic functions by Eph/ephrin signaling. Nat Neurosci. 2009, 12(1): 15-20.