δ-Catenin-induced dendritic morphogenesis: An essential role of p190RhoGEF interaction through AKT1-mediated phosphorylation

College of Pharmacy and Research Institute of Drug Development, Chonnam National University, Gwangju 500-757, Korea.
Journal of Biological Chemistry (Impact Factor: 4.57). 02/2008; 283(2):977-87. DOI: 10.1074/jbc.M707158200
Source: PubMed


Delta-catenin was first identified through its interaction with Presenilin-1 and has been implicated in the regulation of dendrogenesis and cognitive function. However, the molecular mechanisms by which delta-catenin promotes dendritic morphogenesis were unclear. In this study, we demonstrated delta-catenin interaction with p190RhoGEF, and the importance of Akt1-mediated phosphorylation at Thr-454 residue of delta-catenin in this interaction. We have also found that delta-catenin overexpression decreased the binding between p190RhoGEF and RhoA, and significantly lowered the levels of GTP-RhoA but not those of GTP-Rac1 and -Cdc42. Delta-catenin T454A, a defective form in p190RhoGEF binding, did not decrease the binding between p190RhoGEF and RhoA. Delta-catenin T454A also did not lower GTP-RhoA levels and failed to induce dendrite-like process formation in NIH 3T3 fibroblasts. Furthermore, delta-catenin T454A significantly reduced the length and number of mature mushroom shaped spines in primary hippocampal neurons. These results highlight signaling events in the regulation of delta-catenin-induced dendrogenesis and spine morphogenesis.

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Available from: Woo-Joo Song
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    • "Although previous studies suggested that 14-3-3 could be a new partner of δ-catenin [12] [13], the functional significance of the interaction between δ-catenin and 14-3-3 is not completely understood. 14-3-3 Proteins are a highly conserved family of phospho-serine/ threonine binding proteins with molecular weights in the range of 28–33 kD. "
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    ABSTRACT: Accumulated evidence suggests that aberrant regulation of δ-catenin leads to pathological consequences such as mental retardation and cognitive dysfunction. This study revealed that 14-3-3ɛ/ζ stabilizes δ-catenin, with different binding regions involved in the interaction. Furthermore, the specific inhibition of the interaction of 14-3-3 with δ-catenin reduced levels of δ-catenin and significantly impaired the capacity of δ-catenin to induce dendritic branching in both NIH3T3 fibroblasts and primary hippocampal neurons. However, the S1094A δ-catenin mutant, which cannot interact with 14-3-3ζ, still retained the capability of inducing dendrogenesis. Taken together, these results elucidate the underlying events that regulate the stability of δ-catenin and δ-catenin-induced dendrogenesis.
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    • "Another binding partner of 14-3-3ζ is δ-catenin, a brain-specific member of the adherens junction complex that is required for the maintenance of neural structure and implicated in the regulation of cognitive function [59]. The 14-3-3 and δ-catenin interaction was first identified by a yeast twohybrid screen and subsequently confirmed in a follow-up study [60] [61]. Interestingly, δ-catenin also interacts with presenilin-1, which is an important modulator of Wnt signaling during neuronal development and the gene most commonly mutated in early onset familial AD [62]. "
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    ABSTRACT: 14-3-3 proteins were originally discovered as a family of proteins that are highly expressed in the brain. Through interactions with a multitude of binding partners, 14-3-3 proteins impact many aspects of brain function including neural signaling, neuronal development and neuroprotection. Although much remains to be learned and understood, 14-3-3 proteins have been implicated in a variety of neurological disorders based on evidence from both clinical and laboratory studies. Here we will review previous and more recent research that has helped us understand the roles of 14-3-3 proteins in both neurodegenerative and neuropsychiatric diseases.
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    • "Moreover, treatment of neurons with the AMPAR antagonist NBQX decreases forebrain spine density and increases RhoA activity through GEF-H1 [Kang et al., 2009]. d-Catenin, a member of the p120-Catenin subfamily of armadillo proteins , increases spine density by inactivating P190Rho- GEF, a GEF for RhoA [Kim et al., 2008]. "
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    ABSTRACT: Dendritic spines are the sites of most excitatory synapses in the central nervous system. Recent studies have shown that spines function independently of each other, and they are currently the smallest known processing units in the brain. Spines exist in an array of morphologies, and spine structure helps dictate synaptic function. Dendritic spines are rich in actin, and actin rearrangements are critical regulators of spine morphology and density. In this review, we discuss the importance of actin in regulating dendritic spine morphogenesis, and discuss the upstream signal transduction pathways that either foster or inhibit actin polymerization. The understanding of actin regulatory pathways is best conceptualized as a hierarchical network in which molecules function in discrete levels defined by their molecular distance to actin. To this end, we focus on several classes of molecules, including guanine nucleotide exchange factors, small GTPases, small GTPase effectors, and actin binding proteins. We discuss how individual proteins in these molecular classes impact spine morphogenesis, and reveal the biochemical interactions in these networks that are responsible for shaping actin polymerization. Finally, we discuss the importance of these actin regulatory pathways in neuropsychiatric disorders.
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