Essential role of filopodia in chemotropic turning of nerve growth cone induced by a glutamate gradient

Zheng, James; Wan, Jijun; Poo, Mu‐ming

doi:10.1523/jneurosci.16-03-01140.1996

Cited by 292 publications

(255 citation statements)

References 40 publications

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“…Olfactory nerve layers stain moderately for NR1 (Petralia et al, 1994b), and we detect NR2A / B in both main and accessory nerve layers. NMDA receptors promote and regulate neurite outgrowth (Zheng et al, 1996) and play crucial roles in the establishment of neuronal connectivity throughout the brain. If glutamatergic transmission occurs among the thin, unmyelinated (Gr) is not stained for D-serine.…”

Section: Discussionmentioning

confidence: 99%

d-Serine as a Neuromodulator: Regional and Developmental Localizations in Rat Brain Glia Resemble NMDA Receptors

Schell¹,

Brady²,

Molliver³

et al. 1997

J. Neurosci.

391

349

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D-Serine is localized in mammalian brain to a discrete population of glial cells near NMDA receptors, suggesting that D-serine is an endogenous agonist of the receptor-associated glycine site. To explore this possibility, we have compared the immunohistochemical localizations of D-serine, glycine, and NMDA receptors in rat brain. In the telencephalon, D-serine is concentrated in protoplasmic astrocytes, which are abundant in neuropil in close vicinity to NMDA receptor 2A/B subunits. Ultrastructural examination of the CA1 region of hippocampus reveals D-serine in the cytosolic matrix of astrocytes that ensheath neurons and blood vessels, whereas NR2A/B is concentrated in dendritic spines. By contrast, glycine immunoreactivity in telencephalon is the lowest in brain. During postnatal week 2, D-serine levels in cerebellum are comparable to those in adult cerebral cortex but fall to undetectable levels by day 26.During week 2, we observe parallel ontogeny of D-serine in Bergmann glia and NR2A/B in Purkinje cells, suggesting a role for astrocytic D-serine in NMDA receptor-mediated synaptogenesis. D-Serine in the radial processes of Bergmann glia is also well positioned to regulate NMDA receptor-dependent granule cell migration. In the inner granule layer, D-serine is found transiently in protoplasmic astrocytes surrounding glomeruli, where it could regulate development of the mossy fiber/granule cell synapse. D-Serine seems to be the endogenous ligand of glycine sites in the telencephalon and developing cerebellum, whereas glycine predominates in the adult cerebellum, olfactory bulb, and hindbrain. Key words: D-serine; glycine; NMDA receptor; glia; D-amino acid; cerebellumActivation of NMDA receptor channels requires both glutamate and stimulation of a "glycine site" (Johnson and Ascher, 1987;Reynolds et al., 1987;Kemp and Leeson, 1993). Neurophysiological studies of expressed NMDA receptors indicate that with certain combinations of NR1 and NR2 subunits, D-serine is up to three times more potent than glycine at the glycine site (Matsui et al., 1995;Priestley et al., 1995). Although D-amino acids have long been known to exist in bacteria, worms, and insects (Corrigan, 1969), only very recently have high levels of D-serine been demonstrated in mammalian tissues, especially in the brain (Hashimoto et al., 1992a(Hashimoto et al., , 1993aNagata, 1992;Chouinard et al., 1993;Nagata et al., 1994).We have mapped D-serine immunohistochemically in rat brain and observed a pattern that parallels the localization of D-serine binding sites associated with NMDA receptors in the forebrain (Schell et al., 1995). D-Serine is concentrated in gray matter regions enriched in NMDA receptors and is selectively localized to protoplasmic astrocytes. We have also demonstrated that agonists of non-NMDA receptors enhance the efflux of preloaded D-serine from cultures of cortical type 2 astrocytes. These data suggest that D-serine is an endogenous ligand at the glycine site of many NMDA receptors and that glutamate releases D-serine from glial ...

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Section: Discussionmentioning

confidence: 99%

d-Serine as a Neuromodulator: Regional and Developmental Localizations in Rat Brain Glia Resemble NMDA Receptors

Schell¹,

Brady²,

Molliver³

et al. 1997

J. Neurosci.

391

349

View full text Add to dashboard Cite

show abstract

“…Although previous studies strongly suggest glutamate regulates early in vitro neuronal development (Pearce et al 1987;Burgoyne et al 1988;Brewer and Cotman 1989;Rashid and Cambray-Deakin 1992;Zheng et al 1996;Cuppini et al 1999;Heng et al 1999;Chang and De Camilli 2001), NMDARs are thought not to be fully expressed (Zhong et al 1994;Li et al 1998) or functional (Murphy and Baraban 1990;Ujihara and Albuquerque 1992) until 7 DIV. However, other studies suggest that NMDAR subunits are indeed present as early as 1 DIV (Pearce et al 1987;Allen et al 1988;Zhong et al 1994;Heng et al 1995;Lin et al 1997;Li et al 1998;Cuppini et al 1999) and are thought to be functional (Cuppini et al 1999).…”

Section: Regulation Of Neuronal Maturation By Nmda Receptorsmentioning

confidence: 98%

Effects of Disrupting Calcium Homeostasis on Neuronal Maturation: Early Inhibition and Later Recovery

et al. 2008

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It has become increasingly clear that agents that disrupt calcium homeostasis may also be toxic to developing neurons. Using isolated primary neurons, we sought to understand the neurotoxicity of agents such as MK801 (which blocks ligand-gated calcium entry), BAPTA (which chelates intracellular calcium), and thapsigargin (TG; which inhibits the endoplasmic reticulum Ca 2+ -ATPase pump). Thus, E18 at cotical neuons wee grown for 1 day in vitro (DIV) and then exposed to vehicle (0.1% DMSO), MK801 (0.01-20 μM), BAPTA (0.1-20 μM), or TG (0.001-1 μM) for 24 h. We found that all three agents could profoundly influence early neuronal maturation (growth cone expansion, neurite length, neurite complexity), with the order of potency being MK801 < BAPTA < TG. We next asked if cultures exposed to these agents were able to re-establish their developmental program once the agent was removed. When we examined network maturity at 4 and 7 DIV, the order of recovery was MK801 > BAPTA > TG. Thus, mechanistically distinct ways of disrupting calcium homeostasis differentially influenced both short-term and long-term neuronal maturation. These observations suggest that agents that act by altering intracellular calcium and are used in obstetrics or neonatology may be quite harmful to the still-developing human brain.

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“…6 Some works have identified lamellipodia and filopodia as key players in the machinery of cell motion. 7,8 These protrusions are precursors for the establishment of focal contacts eventually acting as mechanosensors for cell motion. 9 On uniformly coated in vitro surfaces, protrusions stochastically fluctuate around the cell edge exploring cell microenvironment seeking for a docking site where to adhere, stabilize and apply forces.…”

Section: Introductionmentioning

confidence: 99%

The cell ratchet: Interplay between efficient protrusions and adhesion determines cell motion

Caballero

Voituriez

Riveline

2015

Cell Adhesion & Migration

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M any physiological and pathological processes involve directed cell motion. In general, migrating cells are represented with a polarized morphology with extending and retracting protrusions at the leading edge. However, cell motion is a more complex phenomenon. Cells show heterogeneous morphologies and high protrusive dynamics is not always related to cell shape. This prevents the quantitative prediction of cell motion and the identification of cellular mechanisms setting directionality. Here we discuss the importance of protrusion fluctuations in directed cell motion. We show how their spatiotemporal distribution and dynamics determine the fluctuations and directions of cell motion for NIH3T3 fibroblasts plated on micro-patterned adhesive ratchets. 1 We introduce efficient protrusions and direction index which capture short-term cell motility over hours: these new read-outs allow the prediction of parameters characteristic for the long-term motion of cells over days. The results may have important implications for the study of biological phenomena where directed cell migration is involved, in morphogenesis and in cancer.

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Essential role of filopodia in chemotropic turning of nerve growth cone induced by a glutamate gradient

Cited by 292 publications

References 40 publications

d-Serine as a Neuromodulator: Regional and Developmental Localizations in Rat Brain Glia Resemble NMDA Receptors

d-Serine as a Neuromodulator: Regional and Developmental Localizations in Rat Brain Glia Resemble NMDA Receptors

Effects of Disrupting Calcium Homeostasis on Neuronal Maturation: Early Inhibition and Later Recovery

The cell ratchet: Interplay between efficient protrusions and adhesion determines cell motion

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