The EphA4 receptor regulates neuronal morphology through SPAR-mediated inactivation of Rap GTPases.

Article Details

Citation

Richter M, Murai KK, Bourgin C, Pak DT, Pasquale EB

The EphA4 receptor regulates neuronal morphology through SPAR-mediated inactivation of Rap GTPases.

J Neurosci. 2007 Dec 19;27(51):14205-15.

PubMed ID
18094260 [ View in PubMed
]
Abstract

Eph receptors play critical roles in the establishment and remodeling of neuronal connections, but the signaling pathways involved are not fully understood. We have identified a novel interaction between the C terminus of the EphA4 receptor and the PDZ domain of the GTPase-activating protein spine-associated RapGAP (SPAR). In neuronal cells, this binding mediates EphA4-dependent inactivation of the closely related GTPases Rap1 and Rap2, which have recently been implicated in the regulation of dendritic spine morphology and synaptic plasticity. We show that SPAR-mediated inactivation of Rap1, but not Rap2, is critical for ephrin-A-dependent growth cone collapse in hippocampal neurons and decreased integrin-mediated adhesion in neuronal cells. Distinctive effects of constitutively active Rap1 and Rap2 on the morphology of growth cones and dendritic spines support the idea that these two GTPases have different functions in neurons. Together, our data implicate SPAR as an important signaling intermediate that links the EphA4 receptor with Rap GTPase function in the regulation of neuronal morphology.

DrugBank Data that Cites this Article

Polypeptides
NameUniProt ID
Ephrin type-A receptor 4P54764Details