<i>In Vivo</i>Trafficking and Targeting of N-Cadherin to Nascent Presynaptic Terminals

Jontes, James D.; Emond, Michelle R.; Smith, Stephen J.

doi:10.1523/jneurosci.5399-04.2004

Cited by 81 publications

(69 citation statements)

References 46 publications

(68 reference statements)

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“…Neuronal processes were classified as growth cones if at any time during the observation period their tips displayed a broad splayed morphology and demonstrated exploratory behavior that consisted of extension, retraction, and turning behaviors. A similar mechanism of en passant synapse formation has been described in the unbranched axons of zebrafish spinal neurons (Jontes et al, 2000(Jontes et al, , 2004 and in hippocampal neurons in vitro (Ahmari et al, 2000). Figure 3A also shows an example of a new branch forming by splitting of an axonal growth cone.…”

Section: Resultssupporting

confidence: 65%

Evidence fromIn VivoImaging That Synaptogenesis Guides the Growth and Branching of Axonal Arbors by Two Distinct Mechanisms

Meyer¹,

Smith²

2006

J. Neurosci.

263

318

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To explore the relationship between axon arbor growth and synaptogenesis, developing retinal ganglion cell (RGC) axon arbors in zebrafish optic tectum were imaged in vivo at high temporal and spatial resolution using two-photon microscopy. Individual RGC axons were dually labeled by expression of a cytosolic red fluorescent protein (DsRed Express) to mark arbor structure and a fusion of the synaptic vesicle protein synaptophysin with green fluorescent protein (Syp:GFP) to mark presynaptic vesicles. Analysis of time-lapse sequences acquired at 10 min intervals revealed unexpectedly rapid kinetics of both axon branch and vesicle cluster turnover. Nascent axonal branches exhibited short average lifetimes of 19 min, and only 17% of newly extended axonal processes persisted for periods exceeding 3 h. The majority (70%) of Syp:GFP puncta formed on newly extended axonal processes. Syp:GFP puncta also exhibited short average lifetimes of 30 min, and only 34% of puncta were stabilized for periods exceeding 3 h. Moreover, strongly correlated dynamics of Syp:GFP puncta and branch structure suggest that synaptogenesis exerts strong influences on both the extension and the selective stabilization of nascent branches. First, new branches form almost exclusively at newly formed Syp:GFP puncta. Second, stabilized nascent branches invariably bear Syp:GFP puncta, and the detailed dynamics of branch retraction suggest strongly that nascent synapses can act at branch tips to arrest retraction. These observations thus provide evidence that synaptogenesis guides axon arbor growth by first promoting initial branch extension and second by selective branch stabilization.

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Section: Resultssupporting

confidence: 65%

Evidence fromIn VivoImaging That Synaptogenesis Guides the Growth and Branching of Axonal Arbors by Two Distinct Mechanisms

Meyer¹,

Smith²

2006

J. Neurosci.

263

318

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“…Molecular-level imaging of receptor fusions in vivo has been limited to mostly transparent organisms such as zebrafish (Jontes et al, 2004). The only dynamic molecular imaging in the LN to date has shown that LAT (linker of activated T cells) localizes to the contact interface during stable interactions of activated T cells with antigen-bearing B cells but not during motile interactions of activated T cells with DCs (Azar et al, 2010).…”

Section: Expression and Functionality Of The Ot-i-gfp Tcrmentioning

confidence: 99%

Real-time analysis of T cell receptors in naive cells in vitro and in vivo reveals flexibility in synapse and signaling dynamics

Friedman¹,

Beemiller²,

Sorensen³

et al. 2010

J Cell Biol

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The real-time dynamics of the T cell receptor (TCR) reflect antigen detection and T cell signaling, providing valuable insight into the evolving events of the immune response. Despite considerable advances in studying TCR dynamics in simplified systems in vitro, live imaging of subcellular signaling complexes expressed at physiological densities in intact tissues has been challenging. In this study, we generated a transgenic mouse with a TCR fused to green fluorescent protein to provide insight into the early signaling events of the immune response. To enable imaging of TCR dynamics in naive T cells in the lymph node, we enhanced signal detection of the fluorescent TCR fusion protein and used volumetric masking with a second fluorophore to mark the T cells expressing the fluorescent TCR. These in vivo analyses and parallel experiments in vitro show minimal and transient incorporation of TCRs into a stable central supramolecular activating cluster (cSMAC) structure but strong evidence for rapid, antigen-dependent TCR internalization that was not contingent on T cell motility arrest or cSMAC formation. Short-lived antigen-independent TCR clustering was also occasionally observed. These in vivo observations demonstrate that varied TCR trafficking and cell arrest dynamics occur during early T cell activation.

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“…Preassembled packets of presynaptic proteins are thought to move along the axon in transport vesicles, and docking and fusion of these vesicles at nascent contacts permits rapid assembly of presynaptic domains [20]. N-cadherin was shown to be a component of these presynaptic packets [9], and is transported along extending axons [10]. Although in epithelial cells β-catenin binding to E-cadherin is required to facilitate E-cadherin targeting to the plasma membrane [21], deletion of the β-catenin binding region in N-cadherin does not inhibit membrane targeting or packet formation in vivo [10].…”

Section: Catenins and The Presynapsementioning

confidence: 99%

“…N-cadherin was shown to be a component of these presynaptic packets [9], and is transported along extending axons [10]. Although in epithelial cells β-catenin binding to E-cadherin is required to facilitate E-cadherin targeting to the plasma membrane [21], deletion of the β-catenin binding region in N-cadherin does not inhibit membrane targeting or packet formation in vivo [10]. This result suggests that β-catenin is not required for N-cadherin trafficking, and that cadherins may function independently of catenins in this initial stage of presynapse formation.…”

Section: Catenins and The Presynapsementioning

confidence: 99%

“…Cadherins are expressed in neurons and are among the first proteins concentrated at nascent excitatory synapses in cultured hippocampal neurons [8]. N-cadherin is transported with early components of the active zone in precursor vesicle packets that initiate synapse formation [9], and N-cadherin colocalizes with early synaptic markers along extending axons in vivo [10]. These observations suggest that cadherins could function in early stages of synapse formation and presynapse assembly.…”

Section: Introductionmentioning

confidence: 99%

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Catenins: playing both sides of the synapse

Kwiatkowski

Weis

Nelson

2007

Current Opinion in Cell Biology

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Synapses of the central nervous system (CNS) are specialized cell-cell junctions that mediate intercellular signal transmission from one neuron to another. The directional nature of signal relay requires that synaptic contacts are morphologically asymmetric with distinct protein components, while changes in synaptic communication during neural network formation require synapses to be plastic. Synapse morphology and plasticity require a dynamic actin cytoskeleton. Classical cadherins, which are junctional proteins associated with the actin cytoskeleton, localize to synapses and regulate synaptic adhesion, stability and remodeling. The major intracellular components of cadherin junctions are the catenin proteins, and increasing evidence suggests that cadherin-catenin complexes modulate an array of synaptic processes. Here we review the role of catenins in regulating the development of pre-and postsynaptic compartments and function in synaptic plasticity, with particular focus on their role in regulating the actin cytoskeleton.

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In VivoTrafficking and Targeting of N-Cadherin to Nascent Presynaptic Terminals

Cited by 81 publications

References 46 publications

Evidence fromIn VivoImaging That Synaptogenesis Guides the Growth and Branching of Axonal Arbors by Two Distinct Mechanisms

Evidence fromIn VivoImaging That Synaptogenesis Guides the Growth and Branching of Axonal Arbors by Two Distinct Mechanisms

Real-time analysis of T cell receptors in naive cells in vitro and in vivo reveals flexibility in synapse and signaling dynamics

Catenins: playing both sides of the synapse

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