EphA4 Signaling Regulates Phospholipase Cγ1 Activation, Cofilin Membrane Association, and Dendritic Spine Morphology

Zhou, Lei; Martinez, Sarah J.; Haber, Michael; Jones, Emma V.; Bouvier, David; Doucet, Guy; Corera, Amadou T.; Fon, Edward A.; Zisch, Andreas H.; Murai, Keith K.

doi:10.1523/jneurosci.1170-07.2007

Cited by 79 publications

(84 citation statements)

References 79 publications

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“…S3o-r). In addition, we found that growth cone collapse coincides with phosphorylation of three potential downstream signalling proteins of EphA4: the guanine nucleotide exchange factor ephexin-1 30 , the actin-depolymerizing and -severing factor cofilin-1 31 and the ATP-dependent motor protein myosin-2 (responsible for actin-based motility) 32 (Fig. 5h,i,j, respectively).…”

Section: Ephrin-a5/epha4 Induces Type I Sgn Growth Cone Collapsementioning

confidence: 84%

Ephrin-A5/EphA4 signalling controls specific afferent targeting to cochlear hair cells

et al. 2013

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Hearing requires an optimal afferent innervation of sensory hair cells by spiral ganglion neurons in the cochlea. Here we report that complementary expression of ephrin-A5 in hair cells and EphA4 receptor among spiral ganglion neuron populations controls the targeting of type I and type II afferent fibres to inner and outer hair cells, respectively. In the absence of ephrin-A5 or EphA4 forward signalling, a subset of type I projections aberrantly overshoot the inner hair cell layer and invade the outer hair cell area. Lack of type I afferent synapses impairs neurotransmission from inner hair cells to the auditory nerve. By contrast, radial shift of type I projections coincides with a gain of presynaptic ribbons that could enhance the afferent signalling from outer hair cells. Ephexin-1, cofilin and myosin light chain kinase act downstream of EphA4 to induce type I spiral ganglion neuron growth cone collapse. Our findings constitute the first identification of an Eph/ephrin-mediated mutual repulsion mechanism responsible for specific sorting of auditory projections in the cochlea.

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Section: Ephrin-a5/epha4 Induces Type I Sgn Growth Cone Collapsementioning

confidence: 84%

Ephrin-A5/EphA4 signalling controls specific afferent targeting to cochlear hair cells

et al. 2013

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“…Organotypic hippocampal slices were prepared as described previously (Zhou et al, 2007). Briefly, 300 m hippocampal slices were prepared from postnatal day 6 (P6) pups and transferred onto semiporous tissue culture inserts (0.4 m pore size; Millipore).…”

Section: Methodsmentioning

confidence: 99%

Astrocytes Control Glutamate Receptor Levels at Developing Synapses through SPARC–β-Integrin Interactions

Jones¹,

Bernardinelli²,

Tse³

et al. 2011

J. Neurosci.

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125

112

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Neurons recruit numerous mechanisms to facilitate the development of synaptic connections. However, little is known about activitydependent mechanisms that control the timing and fidelity of this process. Here we describe a novel pathway used by neurons to regulate glutamate receptors at maturing central synapses. This pathway relies on communication between neurons and astrocytes and the ability of astrocytes to release the factor SPARC (secreted protein, acidic and rich in cysteine). SPARC expression is dynamically regulated and plays a critical role in determining the level of synaptic AMPARs. SPARC ablation in mice increases excitatory synapse function, causes an abnormal accumulation of surface AMPARs at synapses, and impairs synaptic plasticity during development. We further demonstrate that SPARC inhibits the properties of neuronal ␤3-integrin complexes, which are intimately coupled to AMPAR stabilization at synapses. Thus neuron-glial signals control glutamate receptor levels at developing synapses to enable activity-driven modifications of synaptic strength.

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“…For expressing ChR2 in hippocampal slices, Semliki Forest virus (SFV) constructs were created as described previously (Ehrengruber et al, 1999;Haber et al, 2006;Zhou et al, 2007). The vector pCAGGS-ChR2-Venus was obtained from Addgene (Petreanu et al, 2007).…”

Section: Methodsmentioning

confidence: 99%

“…Farnesylated mCherry (mCherry-f) was created by cloning the farnesylation sequence of Ha-Ras onto the C terminus of mCherry (from R. Tsien, Howard Hughes Medical Institute, University of California, San Diego, La Jolla, CA). Genes for ChR2-Venus and mCherry-f were each cloned 3Ј to a viral subgenomic promoter in a modified SFV vector (SFV-PD) (Lundstrom et al, 2003;Zhou et al, 2007). The SFV-PD vector containing eGFP-f alone was described previously (Haber et al, 2006).…”

Section: Methodsmentioning

confidence: 99%

Astrocytes Display Complex and Localized Calcium Responses to Single-Neuron Stimulation in the Hippocampus

Bernardinelli

Salmon²,

Jones³

et al. 2011

Journal of Neuroscience

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Astrocytes show a complex structural and physiological interplay with neurons and respond to neuronal activation in vitro and in vivo with intracellular calcium elevations. These calcium changes enable astrocytes to modulate synaptic transmission and plasticity through various mechanisms. However, the response pattern of astrocytes to single neuronal depolarization events still remains unresolved. This information is critical for fully understanding the coordinated network of neuron-glial signaling in the brain. To address this, we developed a system to map astrocyte calcium responses along apical dendrites of CA1 pyramidal neurons in hippocampal slices using single-neuron stimulation with channelrhodopsin-2. This technique allowed selective neuronal depolarization without invasive manipulations known to alter calcium levels in astrocytes. Light-evoked neuronal depolarization was elicited and calcium events in surrounding astrocytes were monitored using the calcium-sensitive dye Calcium Orange. Stimulation of single neurons caused calcium responses in populations of astrocytes along the apical axis of CA1 cell dendrites. Calcium responses included single events that were synchronized with neuronal stimulation and poststimulus changes in calcium event frequency, both of which were modulated by glutamatergic and purinergic signaling. Individual astrocytes near CA1 cells showed low ability to respond to repeated neuronal depolarization events. However, the response of the surrounding astrocyte population was remarkably accurate. Interestingly, the reliability of responses was graded with respect to astrocyte location along the CA1 cell dendrite, with astrocytes residing in the primary dendrite subregion being most responsive. This study provides a new perspective on the dynamic response property of astrocyte ensembles to neuronal activity.

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EphA4 Signaling Regulates Phospholipase Cγ1 Activation, Cofilin Membrane Association, and Dendritic Spine Morphology

Cited by 79 publications

References 79 publications

Ephrin-A5/EphA4 signalling controls specific afferent targeting to cochlear hair cells

Ephrin-A5/EphA4 signalling controls specific afferent targeting to cochlear hair cells

Astrocytes Control Glutamate Receptor Levels at Developing Synapses through SPARC–β-Integrin Interactions

Astrocytes Display Complex and Localized Calcium Responses to Single-Neuron Stimulation in the Hippocampus

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