Changes in the actin cytoskeleton are a primary mechanism mediating the morphological and functional plasticity that underlies learning and memory. The synaptic Ras homologous (Rho) guanine nucleotide exchange factors (GEFs) Kalirin and Trio have emerged as central regulators of actin dynamics at the synapse. The increased attention surrounding Kalirin and Trio stems from the growing evidence for their roles in the etiology of a wide range of neurodevelopmental and neurodegenerative disorders. In this Review, we discuss recent findings revealing the unique and diverse functions of these paralog proteins in neurodevelopment, excitatory synaptic transmission, and plasticity. We additionally survey the growing literature implicating these proteins in various neurological disorders.
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| http://dx.doi.org/10.1016/j.tins.2020.05.002 | DOI Listing |
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Article Synopsis
- - The RhoGEFs Kalirin-7 and Trio play important roles in synaptic plasticity, and their dysfunction is linked to various neurodevelopmental and neurodegenerative disorders.
- - Through unbiased proteomics, researchers identified the distinct protein interaction networks for Kalirin-7 and Trio, finding that Trio is associated with axon guidance and presynaptic complexes, while Kalirin-7 interacts more with synaptic adhesion proteins.
- - The study highlights Kalirin-7's specific interaction with neuroligin-1 (NLGN1), showing that this interaction is crucial for NLGN1's role in synaptic function, thus unveiling new insights into the mechanisms of these disease-related proteins.
Evolution of the Rho guanine nucleotide exchange factors Kalirin and Trio and their gene expression in Xenopus development.
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Philipps-Universität Marburg, Faculty of Biology, Molecular Embryology, Marburg, Germany; DFG Research Training Group, Membrane Plasticity in Tissue Development and Remodeling, GRK 2213, Philipps-Universität Marburg, Marburg, Germany. Electronic address:
Guanine nucleotide exchange factors (GEFs) activate Rho GTPases by accelerating their GDP/GTP exchange. Trio and its paralog Kalirin (Kalrn) are unique members of the Rho-GEFs that harbor three catalytic domains: two functional GEF domains and a serine/threonine kinase domain. The N-terminal GEF domain activates Rac1 and RhoG GTPases, while the C-terminal GEF domain acts specifically on RhoA.
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