The guanine nucleotide exchange factor (GEF) Asef2 promotes dendritic spine formation via Rac activation and spinophilin-dependent targeting.

The Journal of Biological Chemistry
J Corey EvansDonna J Webb

Abstract

Dendritic spines are actin-rich protrusions that establish excitatory synaptic contacts with surrounding neurons. Reorganization of the actin cytoskeleton is critical for the development and plasticity of dendritic spines, which is the basis for learning and memory. Rho family GTPases are emerging as important modulators of spines and synapses, predominantly through their ability to regulate actin dynamics. Much less is known, however, about the function of guanine nucleotide exchange factors (GEFs), which activate these GTPases, in spine and synapse development. In this study we show that the Rho family GEF Asef2 is found at synaptic sites, where it promotes dendritic spine and synapse formation. Knockdown of endogenous Asef2 with shRNAs impairs spine and synapse formation, whereas exogenous expression of Asef2 causes an increase in spine and synapse density. This effect of Asef2 on spines and synapses is abrogated by expression of GEF activity-deficient Asef2 mutants or by knockdown of Rac, suggesting that Asef2-Rac signaling mediates spine development. Because Asef2 interacts with the F-actin-binding protein spinophilin, which localizes to spines, we investigated the role of spinophilin in Asef2-promoted spine formation. Spi...Continue Reading

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Citations

Jun 11, 2016·Cell Stress & Chaperones·Philip L HooperLászló Vígh
Apr 26, 2019·Mammalian Genome : Official Journal of the International Mammalian Genome Society·Nora BourbiaPatrick M Nolan
Dec 2, 2020·European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology·Iria Brocos-MosqueraAmaia M Erdozain
May 20, 2020·Current Biology : CB·Detlev Arendt
May 23, 2018·ACS Chemical Neuroscience·Michael C EdlerAnthony J Baucum
Mar 18, 2019·Developmental Neuroscience·Sowmyalakshmi RasikaVincent El Ghouzzi

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