Calcium triggers calcineurin-dependent synaptic vesicle recycling in mammalian nerve terminals

Marks, Bruno; McMahon, Harvey T.

doi:10.1016/s0960-9822(98)70297-0

Cited by 251 publications

(234 citation statements)

References 46 publications

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“…Dephosphorylation of dynamin 1 by calcineurin decreases its GTPase activity (Liu et al, 1994) and enhances interaction with its partners . The immunosuppressants CsA and Tacrolimus (FK506) are calcineurin inhibitors reported to inhibit synaptic vesicle recycling, a dynamin 1-controlled event (Marks and McMahon, 1998) and to interfere with podosome organization (Ochoa et al, 2000). We found CsA to dramatically decrease both the number of degrading cells and the total area of degradation.…”

Section: Baldassarre Et Almentioning

confidence: 81%

Dynamin Participates in Focal Extracellular Matrix Degradation by Invasive Cells

Baldassarre

Pompeo

Beznoussenko

et al. 2003

MBoC

183

197

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The degradation of extracellular matrix (ECM) by matrix metalloproteases is crucial in physiological and pathological cell invasion alike. Degradation occurs at specific sites where invasive cells make contact with the ECM via specialized plasma membrane protrusions termed invadopodia. Herein, we show that the dynamin 2 (Dyn2), a GTPase implicated in the control of actindriven cytoskeletal remodeling events and membrane transport, is necessary for focalized matrix degradation at invadopodia. Dynamin was inhibited by using two approaches: 1) expression of dominant negative GTPase-impaired or proline-rich domain-deleted Dyn2 mutants; and 2) inhibition of the dynamin regulator calcineurin by cyclosporin A. In both cases, the number and extension of ECM degradation foci were drastically reduced. To understand the site and mechanism of dynamin action, the cellular structures devoted to ECM degradation were analyzed by correlative confocal light-electron microscopy. Invadopodia were found to be organized into a previously undescribed ECM-degradation structure consisting of a large invagination of the ventral plasma membrane surface in close spatial relationship with the Golgi complex. Dyn2 seemed to be concentrated at invadopodia. INTRODUCTIONDegradation of the extracellular matrix (ECM) is a critical process during cell invasion in both physiological and pathological processes such as morphogenesis, differentiation, cell migration, apoptosis, and tumor invasion (reviewed in Basbaum and Werb, 1996). For example, metastatic tumor cells need to overcome the natural barriers impeding access to vascular or lymphatic pathways and to alter the extracellular environment to allow cancer growth in distant locations (reviewed in Foda and Zucker, 2001). This requires the direct participation of released and exposed proteases such as urokinase-type plasminogen activator, lysosomal proteases, and matrix metalloproteases (MMPs); MMPs in particular are thought to play a major role in the degradation of ECM. To reach the plasma membrane, proteases must be transported and processed by the secretory pathway. Although the mechanisms of release, intracellular trafficking and sorting of lysosomal proteases (reviewed in Dell' Angelica and Payne, 2001) and their regulation (Radons et al., 1994;Baldassarre et al., 2000), have been studied and partly elucidated, surprisingly, much less is known concerning the trafficking of the functionally more crucial MMPs, especially the membrane-bound forms (Hotary et al., 2000). Because the focalized delivery/exposure of MMPs is likely to be a crucial factor in physiological ECM remodeling events and cell invasive behavior (Basbaum and Werb, 1996), a key feature of the trafficking of MMPs is their targeting to specialized plasma membrane structures, where ECM degradation occurs (Chen, 1989;Mueller and Chen, 1991;Chen and Wang, 1999). At the ultrastructural level, these structures have been suggested to consist of 200-nmwide and up to 3-m-long membrane protrusions extending into the matrix (Mueller and Ch...

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Section: Baldassarre Et Almentioning

confidence: 81%

Dynamin Participates in Focal Extracellular Matrix Degradation by Invasive Cells

Baldassarre

Pompeo

Beznoussenko

et al. 2003

MBoC

183

197

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“…To test whether clathrin-dependent endocytosis of NMDA receptors (Vissel et al, 2001;Nong et al, 2003) is also involved in the 5-HT 1A modulation of NMDAR currents, we dialyzed neurons with a dynamin inhibitory peptide that interferes with the binding of amphiphysin with dynamin and therefore prevents endocytosis through clathrin-coated pits (Grabs et al, 1997;Marks and McMahon, 1998). We found that the effect of 8-OH-DPAT was intact in neurons loaded with the dynamin inhibitory peptide (50 M; 21.5 Ϯ 2.1%; n ϭ 4) (Fig.…”

Section: Resultsmentioning

confidence: 99%

Serotonin 5-HT1A Receptors Regulate NMDA Receptor Channels through a Microtubule-Dependent Mechanism

Yuen¹

2005

Journal of Neuroscience

209

197

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The serotonin system and NMDA receptors (NMDARs) in prefrontal cortex (PFC) are both critically involved in the regulation of cognition and emotion under normal and pathological conditions; however, the interactions between them are essentially unknown. Here we show that serotonin, by activating 5-HT 1A receptors, inhibited NMDA receptor-mediated ionic and synaptic currents in PFC pyramidal neurons, and the NR2B subunit-containing NMDA receptor is the primary target of 5-HT 1A receptors. This effect of 5-HT 1A receptors was blocked by agents that interfere with microtubule assembly, as well as by cellular knock-down of the kinesin motor protein KIF17 (kinesin superfamily member 17), which transports NR2B-containing vesicles along microtubule in neuronal dendrites. Inhibition of either CaMKII (calcium/calmodulin-dependent kinase II) or MEK/ERK (mitogen-activated protein kinase kinase/extracellular signalregulated kinase) abolished the 5-HT 1A modulation of NMDAR currents. Biochemical evidence also indicates that 5-HT 1A activation reduced microtubule stability, which was abolished by CaMKII or MEK inhibitors. Moreover, immunocytochemical studies show that 5-HT 1A activation decreased the number of surface NR2B subunits on dendrites, which was prevented by the microtubule stabilizer. Together, these results suggest that serotonin suppresses NMDAR function through a mechanism dependent on microtubule/kinesinbased dendritic transport of NMDA receptors that is regulated by CaMKII and ERK signaling pathways. The 5-HT 1A -NMDAR interaction provides a potential mechanism underlying the role of serotonin in controlling emotional and cognitive processes subserved by PFC.

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“…Internalization is accompanied by dephosphorylation of GluR1 at a PKA phosphorylation site 13 ; however, dephosphorylation of a component of the endocytotic machinery might alternatively be required. Indeed, calcineurin is known to dephosphorylate several proteins involved in endocytosis, including dynamin 24,25 .…”

Section: Activity Drives Removal Of Amparsmentioning

confidence: 99%

Restless AMPA receptors: implications for synaptic transmission and plasticity

Lüscher

Frerking

2001

Trends in Neurosciences

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A central assumption in neurobiology holds that changes in the strength of individual synapses underlie changes in behavior. This concept is widely accepted in the case of learning and memory where LTP and LTD are the most compelling cellular models. It is therefore of great interest to understand, on a molecular level, how the brain regulates the strength of neuronal connections. We review a large body of evidence in support of the very straightforward regulation of synaptic strength by changing the number of postsynaptic receptors, and discuss the molecular machinery required for insertion and removal of AMPA receptors.The hypothesis that insertion of AMPA receptors (AMPARs) underlies the increase of synaptic strength associated with LTP was put forward almost 20 years ago 1 , but was largely ignored until the mid-1990s, resurfacing with quantal analysis of LTP (Ref. 2 ). However, only recently has it become the subject of direct experimental scrutiny.The spark for the myriad of research published in the past few years in the field was experiments conducted independently by two groups 3,4 , in which single connections between CA3 axons and CA1 pyramidal cells in acute hippocampal slices were functionally isolated and in some cases yielded only responses from NMDA receptors (NMDARs) and not AMPARs. Inducing LTP, however, caused the appearance of AMPAR mediated excitatory postsynaptic currents (EPSCs). This led to the proposal that a fraction of 'silent' synapses contain only NMDARs, and thus are functionally inactive at normal resting potential, but maintain the capability to undergo LTP, which would be expressed by AMPAR insertion. Although alternative explanations for these results have been proposed 5,6 , synapses with NMDARs but not AMPARs have now been directly identified anatomically in cultured hippocampal neurons using immunofluorescence 7,8 and with immuno-gold preparations visualized by electron microscopy in hippocampal slices 9-11 .AMPARs move from the cytoplasm to the surface and back again Constitutive recyclingIf LTP expression is caused by postsynaptic AMPAR insertion, it must be the case that AMPARs can be inserted into and removed from the postsynaptic membrane on a relatively rapid time scale. To test this experimentally, CA1 pyramidal cells in acute hippocampal slices * Christian.Luscher@medecine.unige.ch.

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Calcium triggers calcineurin-dependent synaptic vesicle recycling in mammalian nerve terminals

Cited by 251 publications

References 46 publications

Dynamin Participates in Focal Extracellular Matrix Degradation by Invasive Cells

Dynamin Participates in Focal Extracellular Matrix Degradation by Invasive Cells

Serotonin 5-HT1A Receptors Regulate NMDA Receptor Channels through a Microtubule-Dependent Mechanism

Restless AMPA receptors: implications for synaptic transmission and plasticity

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