Mechanisms and Function of Dendritic Exocytosis

Kennedy, Matthew J.; Ehlers, Michael

doi:10.1016/j.neuron.2011.02.032

Cited by 115 publications

(106 citation statements)

References 239 publications

(355 reference statements)

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“…In this context, it is interesting to note that high Ca 2ϩ concentrations trigger SNAREmediated exocytosis in a SNAP25-independent manner (Molgó et al, 1989). Examples of atypical SNARE complexes include complexes containing TI-VAMP during neuritogenesis (Danglot et al, 2010), classical SNARE-independent exocytosis in cochlear hair cells (Nouvian et al, 2011), and atypical SNARE complexdependent exocytosis in dendrites (Kennedy and Ehlers, 2011). Here, we show that the TeNT-insensitive protein TI-VAMP, which has previously been shown to be involved in the formation of neurites (Alberts et al, 2006), associates with the DCC/Sytx1 complex and that loss-of-function of this protein results in abnormal Netrin-1-dependent guidance in vivo.…”

Section: Discussionmentioning

confidence: 99%

A Signaling Mechanism Coupling Netrin-1/Deleted in Colorectal Cancer Chemoattraction to SNARE-Mediated Exocytosis in Axonal Growth Cones

et al. 2011

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Directed cell migration and axonal guidance are essential steps in neural development. Both processes are controlled by specific guidance cues that activate the signaling cascades that ultimately control cytoskeletal dynamics. Another essential step in migration and axonal guidance is the regulation of plasmalemma turnover and exocytosis in leading edges and growth cones. However, the cross talk mechanisms linking guidance receptors and membrane exocytosis are not understood. Netrin-1 is a chemoattractive cue required for the formation of commissural pathways. Here, we show that the Netrin-1 receptor deleted in colorectal cancer (DCC) forms a protein complex with the t-SNARE (target SNARE) protein Syntaxin-1 (Sytx1). This interaction is Netrin-1 dependent both in vitro and in vivo, and requires specific Sytx1 and DCC domains. Blockade of Sytx1 function by using botulinum toxins abolished Netrin-1-dependent chemoattraction of axons in mouse neuronal cultures. Similar loss-offunction experiments in the chicken spinal cord in vivo using dominant-negative Sytx1 constructs or RNAi led to defects in commissural axon pathfinding reminiscent to those described in Netrin-1 and DCC loss-of-function models. We also show that Netrin-1 elicits exocytosis at growth cones in a Sytx1-dependent manner. Moreover, we demonstrate that the Sytx1/DCC complex associates with the v-SNARE (vesicle SNARE) tetanus neurotoxin-insensitive vesicle-associated membrane protein (TI-VAMP) and that knockdown of TI-VAMP in the commissural pathway in the spinal cord results in aberrant axonal guidance phenotypes. Our data provide evidence of a new signaling mechanism that couples chemotropic Netrin-1/DCC axonal guidance and Sytx1/TI-VAMP SNARE proteins regulating membrane turnover and exocytosis.

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Section: Discussionmentioning

confidence: 99%

A Signaling Mechanism Coupling Netrin-1/Deleted in Colorectal Cancer Chemoattraction to SNARE-Mediated Exocytosis in Axonal Growth Cones

et al. 2011

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“…It is presumably this mobile pool of AMPARs that allows for rapid but sustained changes in synaptic efficacy. The insertion and removal of AMPARs during LTP and LTD, respectively, is believed to involve classical mechanisms of SNARE protein -mediated exocytosis and dynamin-dependent endocytosis via clathrin-coated vesicles (Lüscher et al 1999;Carroll et al 2001;Kennedy and Ehlers 2011). Current evidence favors the idea that the endocytosis and exocytosis of AMPARs during LTD and LTP happens not directly at the synapse but at slightly perisynaptic locations, from where the receptors reach the postsynaptic density by lateral diffusion.…”

Section: Expression Mechanismmentioning

confidence: 99%

NMDA Receptor-Dependent Long-Term Potentiation and Long-Term Depression (LTP/LTD)

Lüscher¹,

Malenka²

2012

Cold Spring Harbor Perspectives in Biology

857

647

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Long-term potentiation and long-term depression (LTP/LTD) can be elicited by activating N-methyl-D-aspartate (NMDA)-type glutamate receptors, typically by the coincident activity of pre-and postsynaptic neurons. The early phases of expression are mediated by a redistribution of AMPA-type glutamate receptors: More receptors are added to potentiate the synapse or receptors are removed to weaken synapses. With time, structural changes become apparent, which in general require the synthesis of new proteins. The investigation of the molecular and cellular mechanisms underlying these forms of synaptic plasticity has received much attention, because NMDA receptor-dependent LTP and LTD may constitute cellular substrates of learning and memory.L ong-term synaptic plasticity is a generic term that applies to a long-lasting experience-dependent change in the efficacy of synaptic transmission. Here we will focus on N-methyl-D-aspartate (NMDA) receptor-dependent synaptic potentiation (LTP) and depression (LTD), two forms of activity-dependent long-term changes in synaptic efficacy that have been extensively studied. Because both LTP and LTD are believed to represent cellular correlates of learning and memory, they have attracted considerable interest. In this article we will focus on the molecular and cellular mechanisms associated with LTP and LTD. As for other forms of long-term synaptic plasticity, a characterization of LTP and LTD involves describing the molecular mechanisms that are required to elicit the change (induction), followed by an investigation of the mechanism of expression (hours) and maintenance (days). The best-characterized form of NMDA receptor (NMDAR)-dependent LTP occurs between CA3 and CA1 pyramidal neurons of the hippocampus (Fig. 1). Throughout the chapter we will mostly refer to this specific form of LTP. At these CA3-CA1 Schaffer collateral synapses, the loci of both induction and expression are situated in the postsynaptic neuron. AMPA-TYPE AND NMDA-TYPE GLUTAMATE RECEPTORSAfter exocytotic release of the content of the synaptic vesicle from the presynaptic specialization (see Castillo 2012), the neurotransmitter

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“…Interestingly, the presence of smooth ER-derived organelles associated with small vesicular structures raises the possibility that some exocytotic vesicles can be developed directly from dendritic ER elements, bypassing the Golgi apparatus (38,41). Although this straight route of secretory organelles to plasma membrane in dendrites has so far received little functional evidence, with targeting proteins remaining essentially unknown, if true it would represent a unique, noncanonical intracellular vesicle flow pathway that could explain how membrane proteins and peptides get locally trafficked in dendrites lacking Golgi outposts (42). In addition to secretory vesicles, several other exocytotic organelles, including early endosomes, recycling endosomes, late endosomes, and lysosomes, have been identified in dendrites of various neuron types, extensively reviewed recently (42,43).…”

Section: Dendritic Secretory Organellesmentioning

confidence: 99%

“…Nevertheless, specific SNAREs have been assigned to most of the fusion steps and organelle types (18), with illustrative examples of such specialization in neuronal dendrites represented by syntaxin 4 and SNAP-23 (72,73). Highly enriched in dendritic spines, these SNAREs are known to mediate dendritespecific fusion reactions, reviewed in detail recently (42).…”

Section: Secretion From Dendrites Of Central Neurons Relies On Snaresmentioning

confidence: 99%

Dendritic SNAREs add a new twist to the old neuron theory

Ovsepian

Dolly

2011

Proc. Natl. Acad. Sci. U.S.A.

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Dendritic exocytosis underpins a broad range of integrative and homeostatic synaptic functions. Emerging data highlight the essential role of SNAREs in trafficking and fusion of secretory organelles with release of peptides and neurotransmitters from dendrites. This Perspective analyzes recent evidence inferring axo-dendritic polarization of vesicular release machinery and pinpoints progress made with existing challenges in this rapidly progressing field of dendritic research. Interpreting the relation of new molecular data to physiological results on secretion from dendrites would greatly advance our understanding of this facet of neuronal mechanisms.dendritic release | neuronal polarization | retrograde transmission

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Mechanisms and Function of Dendritic Exocytosis

Cited by 115 publications

References 239 publications

A Signaling Mechanism Coupling Netrin-1/Deleted in Colorectal Cancer Chemoattraction to SNARE-Mediated Exocytosis in Axonal Growth Cones

A Signaling Mechanism Coupling Netrin-1/Deleted in Colorectal Cancer Chemoattraction to SNARE-Mediated Exocytosis in Axonal Growth Cones

NMDA Receptor-Dependent Long-Term Potentiation and Long-Term Depression (LTP/LTD)

Dendritic SNAREs add a new twist to the old neuron theory

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