Integrin-type signaling has a distinct influence on NMDA-induced cytoskeletal disassembly

Bahr, Ben A.

doi:10.1002/(sici)1097-4547(20000315)59:6<827::aid-jnr15>3.0.co;2-q

Cited by 27 publications

(20 citation statements)

References 46 publications

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“…ECM signaling at the mammalian NMJ also acts via the ␣/␤-dystroglycan-glycoprotein complex (DGC) (Henry and Campbell 1996;Grady et al 2000). Numerous integrin receptors localize to mammalian NMJs and central glutamatergic synapses, and integrin-ECM interactions regulate aspects of synaptic development and modulation, including glutamatergic transmission and plasticity (Bahr et al 1997;Staubli et al 1998;Bahr 2000;Chavis and Westbrook 2001;Chan et al 2003Chan et al , 2006Kramar et al 2003Kramar et al , 2006Lin et al 2003;Bernard-Trifilo et al 2005;Shi and Ethell 2006;Webb et al 2006Webb et al , 2007.…”

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confidence: 59%

Presynaptic establishment of the synaptic cleft extracellular matrix is required for post-synaptic differentiation

Rohrbough

Rushton²,

Woodruff³

et al. 2007

Genes Dev.

106

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Formation and regulation of excitatory glutamatergic synapses is essential for shaping neural circuits throughout development. In a Drosophila genetic screen for synaptogenesis mutants, we identified mind the gap (mtg), which encodes a secreted, extracellular N-glycosaminoglycan-binding protein. MTG is expressed neuronally and detected in the synaptic cleft, and is required to form the specialized transsynaptic matrix that links the presynaptic active zone with the post-synaptic glutamate receptor (GluR) domain. Null mtg embryonic mutant synapses exhibit greatly reduced GluR function, and a corresponding loss of localized GluR domains. All known post-synaptic signaling/scaffold proteins functioning upstream of GluR localization are also grossly reduced or mislocalized in mtg mutants, including the dPix-dPak-Dock cascade and the Dlg/PSD-95 scaffold. Ubiquitous or neuronally targeted mtg RNA interference (RNAi) similarly reduce post-synaptic assembly, whereas post-synaptically targeted RNAi has no effect, indicating that presynaptic MTG induces and maintains the post-synaptic pathways driving GluR domain formation. These findings suggest that MTG is secreted from the presynaptic terminal to shape the extracellular synaptic cleft domain, and that the cleft domain functions to mediate transsynaptic signals required for post-synaptic development.[Keywords: Glutamatergic synaptogenesis; post-synaptic density; glutamate receptor; secretion; Drosophila; neuromuscular junction] Supplemental material is available at http://www.genesdev.org.

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mentioning

confidence: 59%

Presynaptic establishment of the synaptic cleft extracellular matrix is required for post-synaptic differentiation

Rohrbough

Rushton²,

Woodruff³

et al. 2007

Genes Dev.

106

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“…Anti-BDP^ immunocytochemistr>' was used to localize the spectrin breakdown fragments in sections from slice cultures as described elsewhere (Bahr, 2000). Slices were rinsed with 0.1 M phosphate buffer (PB), pH 7.4, and fixed for 2 hr in cold PB plus 4% paraformaldehyde.…”

Section: Methodsmentioning

confidence: 99%

“…3, bottom). In addition to cytoskeletal damage, excitotoxic slices exhibited corresponding synaptic deterioration, as previously indicated (Bahr, 2000;. For Figure 4 (bottom), the a-keto amide CX295 was preincubated to show that blockage of calpain not only produces cytoskel- etal protection but also attenuates the loss of the presynaptic marker synaptophysin evident 3 hr postinsult.…”

Section: Nmda Was Infused Into Cultured Hippocampal Slicesmentioning

confidence: 99%

“…This is important insofar as calpain is a prominent signaling element involved in multiple pathways implicated in cytoskeletal organization (Huttenlocher et al, 1997;Kawasaki et al, 1997;Bahr, 2000), adhesion responses (Fox et al, 1993;Cooray et al, 1996;Rock et al, 1997;Bahr, 2000), intracellular signals (see Saido et al, 1994;Cooray et al, 1996), and gene regulation (Shumway et al, 1999;Chen et al, 2000;Schoonbroodt et al, 2000). To be effective, therapeutic intervention of calpain actions must not include down-regulation of compensator}' responses needed for survival.…”

Section: Nmda -Cx295 -mentioning

confidence: 99%

“…Blots were also stained for tubulin and with monoclonal anti-ERKl/ERK2 (Zymed Laboratories, South San Francisco, CA) to detemiine total ERK levels and ensure that equal protein was loaded. Integrated density of the bands was determined with Bioquant software (R & M Biometrics, Nashville, TN) after being scanned at high resolution, and the means ± SEM were compared using unpaired, two-tailed Mests or ANOVA.Anti-BDP^ immunocytochemistr>' was used to localize the spectrin breakdown fragments in sections from slice cultures as described elsewhere (Bahr, 2000). Slices were rinsed with 0.1 M phosphate buffer (PB), pH 7.4, and fixed for 2 hr in cold PB plus 4% paraformaldehyde.…”

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Comparison of Novel and Known Neuroprotectants for Treating Exposure to Different Types of Toxins

Bahr¹

2000

Self Cite

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SUPPLEMENTARY NOTESreport contains color Studies using cultured brain slices have found that compensatory signals are activated in response to different types of excitotoxicity/seizures related to environmental toxin or military threat agent exposure. Surprisingly, glutamate receptors, cannabinoid receptors, and proteoglycan-binding adhesion receptors activated common pathways involving MAP kinase, focal adhesion kinase (FAK), and transcription factors that facilitate endogenous repair mechanisms. Inhibition of the receptors potentiated excitotoxic vulnerability and, correspondingly, promoting receptor-mediated responses enhanced cellular and synaptic repair. The receptors seem to act through transcription regulators to explain common signaling elements including MAPK and FAK. NF-KB is one such regulator, activated in response to both excitotoxicity and receptor activation. Interestingly, NF-KB activation is biphasic; properties of the initial phase are consistent with neuroprotection and the second phase with neurodegeneration. Microarray analyses have confirmed that genes activated initially are those that promote survival, while genes activated during the delayed phase can enhance neuronal vulnerability. The latter phase may explain why months after an insult, select brain regions remaui acutely vulnerable to stroke events and age-related neurodegeneration. Studies with receptor modulators are helping to identify key signal transduction pathways that lead to neuroprotection vs. those that enhance neuronal vulnerability, and what determines the direction of the signaling path. SUBJECT TERMS INTRODUCTIONOur previous work has found that excessive glutamatergic activity plays a major role in excitotoxic damage related to environmental toxin or military threat agent exposure. As expected, negative modulation of glutamate receptor activity through antagonists promotes protection against excitotoxic insults (see Buchan et al, 1991;Nellgard and Wieloch, 1992;Sheardown et al., 1993). Interestingly, low-level stimulation of AMPA-type glutamate receptors has been shown to enhance neuronal survival and promote synaptic maintenance (Bambrick et al, 1995;McKinney et al, 1999). This is likely related to the fact that besides having ionotropic properties, AMPA receptors are linked to the neuroprotective mitogen-activated protein kinase (MAPK) pathway (Wang and Durkin, 1995;Hayashi et al., 1999;Limatola et al., 2002). This signaling pathway can be enhanced by the positive modulators call Ampakines , thereby implicating the pathway in Ampakine induction of neurotrophic factor expression (Lauterbom et al, 2000) and neuroprotection agamst stroke-type excitotoxicity . Recent findings indicate that multiple receptor systems are linked to such endogenous repair mechanisms that are responsible for compensatory responses to injury.AMPA receptors are known to participate in higher cognitive fiinctions in the mammalian brain. Positive modulation of AMPA receptors by the Ampakine class of compounds selectively improves channel function...

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Polarized distribution of α5 integrin in dendrites of hippocampal and cortical neurons

Lynch

Zhou

et al. 2001

J of Comparative Neurology

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The distribution of immunoreactivity for the alpha5 subunit of the fibronectin receptor was evaluated in adult rat brain with particular interest in the cellular localization of immunostaining in the hippocampal formation and neocortex. Beyond localization to neuronal perikarya and short dendritic fragments within most brain areas, alpha5 immunoreactivity (-ir) was particularly dense within primary apical dendrites of pyramidal cells in both hippocampus and neocortex and within the dendritic arbors of cerebellar Purkinje cells. In hippocampal and cortical pyramidal cells, immunostaining was clearly polarized: alpha5-ir was not detectable in basal dendrites in hippocampal neurons and was limited to proximal arbors or absent from basal dendrites in pyramidal cells in superficial and deep layers of neocortex. Beyond this, alpha5-ir was distributed within the dendritic ramifications of the dentate gyrus granule cells and within perikarya and dendrites of occasional nonpyramidal neurons. Developmental studies demonstrated that, in both hippocampus and neocortex, alpha5-ir appears first within perikarya and is distributed to dendrites during the second postnatal week. These results are in accord with the broad hypothesis that integrins contribute to apical-basal differences in dendrites and that the integrin fibronectin (alpha5beta1) receptor, in particular, contributes to some late developing features of dendritic structure or function.

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Integrin-type signaling has a distinct influence on NMDA-induced cytoskeletal disassembly

Cited by 27 publications

References 46 publications

Presynaptic establishment of the synaptic cleft extracellular matrix is required for post-synaptic differentiation

Presynaptic establishment of the synaptic cleft extracellular matrix is required for post-synaptic differentiation

Comparison of Novel and Known Neuroprotectants for Treating Exposure to Different Types of Toxins

Polarized distribution of α5 integrin in dendrites of hippocampal and cortical neurons

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