Multiple EphB receptor tyrosine kinases shape dendritic spines in the hippocampus

Henkemeyer, Mark; Itkis, Olga S.; Ngo, Michelle; Hickmott, P. W.; Ethell, Iryna M.

doi:10.1083/jcb.200306033

Cited by 266 publications

(264 citation statements)

References 35 publications

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“…The ability to modulate Rho-GTPase activity in neurons is critical during development to regulate neurite outgrowth, growth cone collapse, and axon guidance [87], and, more recently, as regulators of excitatory synapse formation, function, and plasticity in the central nervous system [88]. Indeed, several EphR and ligands localize with postsynaptic density marker PSD95 at excitatory synapses in hippocampal neurons, including EphA4, EphB1, EphB2, and EphB3 [90][91][92][93][94][95]. To date, at least 2 EphRs have been linked to AD.…”

Section: Erythropoietin-producing Hepatocellular Receptor Signalingmentioning

confidence: 99%

Reversing Synapse Loss in Alzheimer's Disease: Rho-Guanosine Triphosphatases and Insights from Other Brain Disorders

Lefort

2015

Neurotherapeutics

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Alzheimer's disease (AD) is a monumental public health crisis with no effective cure or treatment. To date, therapeutic strategies have focused almost exclusively on upstream signaling events in the disease, namely on β-amyloid and amyloid precursor protein processing, and have, unfortunately, yielded few, if any, promising results. An alternative approach may be to target signaling events downstream of β-amyloid and even tau. However, with so many pathways already linked to the disease, understanding which ones are "drivers" versus "passengers" in the pathogenesis of the disease remains a tremendous challenge. Given the critical roles of Rho-guanosine triphosphatases (GTPases) in regulating the actin cytoskeleton and spine dynamics, and the strong association between spine abnormalities and cognition, it is not surprising that mutations in a number of genes involved in RhoGTPase signaling have been implicated in several brain disorders, including schizophrenia and autism. And now, there is mounting literature implicating Rho-GTPase signaling in AD pathogenesis as well. Here, I review this evidence, with a particular emphasis on the regulators of Rho-GTPase signaling, namely guanine nucleotide exchange factors and GTPaseactivating proteins. Several of these have been linked to various aspects of AD, and each offers a novel potential therapeutic target for AD.

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Section: Erythropoietin-producing Hepatocellular Receptor Signalingmentioning

confidence: 99%

Reversing Synapse Loss in Alzheimer's Disease: Rho-Guanosine Triphosphatases and Insights from Other Brain Disorders

Lefort

2015

Neurotherapeutics

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“…Changes in hippocampal spine density and dimensions occur in several mental disorders, including depression, schizophrenia and addiction. Another study has shown that EphB1, EphB2, and EphB3 are involved all three, although to varying degrees, in dendritic spine morphogenesis and synapse formation in the hippocampus (Henkemeyer et al, 2003). All these candidates are up regulated in that region in all protocols of drug administration…”

Section: Eph Receptors and Related Ephrin Ligands Display Significantmentioning

confidence: 99%

Cocaine-induced expression changes of axon guidance molecules in the adult rat brain

Bahí

Dreyer

2005

Molecular and Cellular Neuroscience

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Administration of drugs of abuse induces strong molecular adaptations and plasticity within the mesolimbic dopamine (DA) system, a pathway essential for reward-seeking behavior. Little is known about the specific targets involved in this neuroadaptation process, but there are indications that cocaine and other drugs of abuse share the ability to alter the morphology of neuronal dendrites and spines, the primary site of excitatory synapses in the brain. Axon guidance molecules, the very molecular cues that regulate the formation of axon-target connections during development, may mediate these alterations. To test this hypothesis, we investigated mRNA expression changes of 39 axon guidance molecules, including 17 Semaphorins, 12 Ephs, 8 Ephrins and 2 neuropilins in the mesolimbic dopamine system of cocaine-treated animals under different paradigms by mean of DNA-Microarray and quantitative real-time PCR. In all cases, strong changes in gene expression are observed, yielding to up or down-regulation of these axon guidance molecules. Our data suggest that cocaine treatment induces activation of a complex program of synaptic rearrangements, which may partly recapitulate the plastic changes occurring during development, and may underlie the important neuroplastic adaptations that occur in the reward-and memory-related brain centers following drug action. We conclude that in some brain regions, exposure to psychomotor-stimulant drugs produce expression changes in axon guidance molecules, which may contribute to cognitive deficits associated with drug abuse.2

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“…Immunolabeling of Eph receptors confirmed their localization in dendritic shafts, filopodial protrusions, and spine heads [45,57,68]. Henkemeyer and colleagues observed that in EphB1/B2-and EphB1/B2/B3-deficient mice, dendritic spines failed to develop [34]. F-actin rich spines were replaced by thin filopodia-shaped protrusions that lacked clustered F-actin.…”

Section: Eph Receptors and Spine Morphogenesismentioning

confidence: 91%

Bidirectional ephrin/Eph signaling in synaptic functions

Aoto¹,

Chen²

2007

Brain Research

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Eph receptors, the largest family of receptor tyrosine kinases, and their membrane bound ligands, the ephrins, are involved in multiple developmental and adult processes within and outside of the nervous system. Bi-directional signaling from both the receptor and the ligand is initiated by ephrinEph binding upon cell-cell contact, and involves interactions with distinct subsets of downstream signaling molecules related to specific functions. In the CNS, Ephs and ephrins act as attractive/ repulsive, migratory, and cell adhesive cues during development and participate in synaptic functions in adult animals. In this review, we will focus on recent findings highlighting the functions of ephrin/ Eph signaling in dendritic spine morphogenesis, synapse formation, and synaptic plasticity.

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Multiple EphB receptor tyrosine kinases shape dendritic spines in the hippocampus

Cited by 266 publications

References 35 publications

Reversing Synapse Loss in Alzheimer's Disease: Rho-Guanosine Triphosphatases and Insights from Other Brain Disorders

Reversing Synapse Loss in Alzheimer's Disease: Rho-Guanosine Triphosphatases and Insights from Other Brain Disorders

Cocaine-induced expression changes of axon guidance molecules in the adult rat brain

Bidirectional ephrin/Eph signaling in synaptic functions

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