Eph receptors and ephrins in neuron–astrocyte communication at synapses

Abstract

Neuron-glia communication is essential for regulating the properties of synaptic connections in the brain. Astrocytes, in particular, play a critical and complex role in synapse development, maintenance, and plasticity. Likewise, neurons reciprocally influence astrocyte physiology. However, the molecular signaling events that enable astrocytes and neurons to effectively communicate with each other are only partially defined. Recent findings have revealed that Eph receptor tyrosine kinases and ephrins play an important role in contact-dependent neuron-glia communication at synapses. Upon binding, these two families of cell surface-associated proteins trigger bidirectional signaling events that regulate the structural and physiological properties of both neurons and astrocytes. This review will focus on the emerging role of Eph receptors and ephrins in neuron-astrocyte interaction at synapses and discuss implications for synaptic plasticity, behavior, and disease.

Impact of traumatic brain injury on sleep structure, electrocorticographic activity and transcriptome in mice

“…In fact, the lack of EphA4 was shown to be positively associated with neuronal reconstruction after spinal cord injury (Goldshmit et al, 2004), likely because EphA4 can mediate spine retraction (Murai and Pasquale, 2011). Importantly, EphA4 and EfnA3 have both been implicated in synaptic plasticity and neuron-glia interactions (Murai and Pasquale, 2011), emphasizing the relevance of changes in these elements after TBI. In the hippocampus, our observation that the expression of the plasticity elements Arc and EfnA3 are restored to Sham levels in mTBI mice that were submitted to SD may also suggest a potential benefit of SD after injury.…”

“…In addition to plasticity genes linked to sleep homeostasis (i.e., Arc, Bdnf, Fos, Homer1a), Ephrins and Eph receptors seemed particularly relevant because of their role in synaptic plasticity and their altered expression after TBI (Hånell et al, 2012;Murai and Pasquale, 2011;Theus et al, 2010). The latter also applies to Hif1a (Higashida et al, 2011).…”

Blockade of EphA4 signaling ameliorates hippocampal synaptic dysfunctions in mouse models of Alzheimer’s disease

“…EphB enhances synapse development via its interaction with NMDA receptors (13), whereas EphA4, which is mainly expressed in the adult hippocampus, acts as a negative regulator of neurotransmission and hippocampal synaptic plasticity (14). EphA4 activation by its ligands, ephrins, triggers forward signaling (12) that leads to the retraction of dendritic spines via cyclin-dependent kinase 5 (Cdk5)-dependent RhoA activation and reduced cell adhesion (15)(16)(17).…”

“…Interestingly, AD patients with only mild cognitive deficits exhibit deregulated EphB and EphA4 expression (20). Given that EphA4 activation results in dendritic spine loss and reduced AMPA receptor abundance (14,19,21), which are potential mechanisms that underlie synaptic dysfunctions in AD (6,8), we investigated the possible link between EphA4 signaling and Aβ-induced synaptic failure.…”

Perisynaptic astroglial processes: dynamic processors of neuronal information

“…Astroglial processes tend to make closer contacts with the postsynaptic rather than presynaptic element (Lehre and Rusakov 2002) and, in this regard, are further enriched with a repertoire of transmembrane and membrane-anchored proteins supporting bidirectional neuroglial signaling. For instance, dendritic spines express Eph receptor tyrosine kinases, while PAPs contain ephrin cell-surface ligands (Murai and Pasquale 2011), together with c-protocadherin (Garrett and Weiner 2009) and most likely integrin receptors (Hama et al 2004;Herrera-Molina et al 2012) (Fig. 2).…”