A post-docking role for active zone protein Rim

Koushika, Sandhya P.; Richmond, Janet E.; Hadwiger, Gayla; Weimer, Robby M.; Jørgensen, Erik M.; Nonet, Michael L.

doi:10.1038/nn732

Cited by 302 publications

(342 citation statements)

References 41 publications

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“…Interestingly, proteins of the presynaptic active zone are properly localized in unc-104 mutants. Specifically, liprin/ SYD-2 (Zhen and Jin, 1999), Rab-3 interacting molecule/ UNC-10 ( Koushika et al, 2001), and RPM-1 (Schaefer et al, 2000;Zhen et al, 2000) are correctly localized in the dorsal cord; however, these incomplete synapses cannot direct the clustering of GABA receptors. Therefore, sites of presynaptic differentiation can be specified in the motor neuron independently from the formation of synaptic vesicle aggregates.…”

Section: The Differentiation Of Gabaergic Neuromuscular Junctions Resmentioning

confidence: 98%

GABA Is Dispensable for the Formation of Junctional GABA Receptor Clusters inCaenorhabditis elegans

Gally

Bessereau

2003

J. Neurosci.

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At GABAergic synapses, GABA receptors form high-density clusters opposite GABA release sites. Whether GABA release per se plays a role in the formation of GABA receptor clusters remains uncertain. To address this question in vivo, we characterized GABA receptor clustering in the nematode Caenorhabditis elegans. In C. elegans, body wall muscles receive excitatory inputs from cholinergic motor neurons and inhibitory inputs from GABAergic neurons. Using immunohistochemistry and green fluorescent protein-tagged proteins, we observed that the muscle GABA receptor UNC-49 is precisely clustered opposite GABA release sites. During development, these clusters appear slightly after the detection of presynaptic vesicles. If motor axons are mislocalized as in unc-5 mutants, GABA receptors cluster opposite ectopic axons at GABA release sites. Together, these data imply that a motor neuron-derived factor is instructing GABA receptor clustering. Presynaptic localization of this clustering activity requires the neuronal kinesin UNC-104, suggesting that release of GABA from synaptic vesicles may represent the clustering signal. However, unc-25 mutants do not synthesize GABA but do cluster postsynaptic GABA receptors indistinguishably from the wild type. Therefore, at GABAergic neuromuscular junctions, GABA receptor clustering requires nerve-muscle interaction but not GABA neurotransmission.

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Section: The Differentiation Of Gabaergic Neuromuscular Junctions Resmentioning

confidence: 98%

GABA Is Dispensable for the Formation of Junctional GABA Receptor Clusters inCaenorhabditis elegans

Gally

Bessereau

2003

J. Neurosci.

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“…These include the ATP-dependent synthesis of phosphoinositides and protein kinase-mediated protein phosphorylation (Klenchin & Martin 2000). More recently, the presynaptic proteins munc-13 and Rim (Rab3-interacting molecule) have also been implicated in priming, mainly because they act after docking but before fusion (Ashery et al 2000;Koushika et al 2001).…”

Section: Docking Priming Atp-dependence and Kinetics Of Exocytosismentioning

confidence: 99%

Mechanisms of Exocytosis in Insulin‐Secreting B‐Cells and Glucagon‐Secreting A‐Cells

Barg

2003

Pharmacology & Toxicology

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In pancreatic B-and A-cells, metabolic stimuli regulate biochemical and electrical processes that culminate in Ca 2π -influx and release of insulin or glucagon, respectively. Like in other (neuro)endocrine cells, Ca 2π -influx triggers the rapid exocytosis of hormone-containing secretory granules. Only a small fraction of granules (Ͻ1% in insulin-secreting B-cells) can be released immediately, while the remainder requires translocation to the plasma membrane and further ''priming'' for release by several ATP-and Ca 2π -dependent reactions. Such functional organization may account for systemic features such as the biphasic time course of glucose-stimulated insulin secretion. Since this release pattern is altered in type-2 diabetes mellitus, it is conceivable that disturbances in the exocytotic machinery underlie the disease. Here I will review recent data from our laboratory relevant for the understanding of these processes in insulin-secreting B-cells and glucagon-secreting A-cells and for the identification of novel targets for antidiabetic drug action. Two aspects are discussed in detail: 1) The importance of a tight interaction between L-type Ca 2π -channels and the exocytotic machinery for efficient secretion; and 2) the role of intragranular acidification for the priming of secretory granules and its regulation by a granular 65-kDa sulfonylurea-binding protein.

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“…Protein components of the vesicle membranes (synaptobrevin, SNB) and plasma membranes [syntaxin and SNAP-25 (synaptosome-associated protein of 25 kDa)] form a SNARE complex that functions as a minimal fusion machine to drive vesicle fusion (3)(4)(5). The formation and conformational change of the SNARE complex requires modulation by other proteins (6)(7)(8)(9). Synaptotagmin (SNT) is a vesicle membrane protein that binds to Ca 2ϩ and forms complexes with phospholipids and SNARE complexes.…”

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confidence: 99%

The C2H2 zinc-finger protein SYD-9 is a putative posttranscriptional regulator for synaptic transmission

Wang

Gracheva

Richmond

et al. 2006

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

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Communication between neurons is largely achieved through chemical synapses, where neurotransmitters are released from synaptic vesicles at presynaptic terminals to activate postsynaptic cells. Exo-and endocytosis are coordinated to replenish the synaptic vesicle pool for sustained neuronal activity. We identified syd-9 (syd, synapse defective), a gene that encodes multiple C2H2 zinc-finger domain-containing proteins specifically required for synaptic function in Caenorhabditis elegans. syd-9 loss-of-function mutants exhibit locomotory defects, a diffuse distribution of synaptic proteins, and decreased synaptic transmission with unaffected neurodevelopment. syd-9 mutants share phenotypic and ultrastructural characteristics with mutants that lack synaptic proteins that are required for endocytosis. syd-9 mutants also display genetic interactions with these endocytotic mutants, suggesting that SYD-9 regulates endocytosis. SYD-9 proteins are enriched in the nuclei of both neuron and muscle cells, but their neuronal expression plays a major role in locomotion. SYD-9 isoforms display a speckle-like expression pattern that is typical of RNAbinding proteins that regulate premRNA splicing. Furthermore, syd-9 functions in parallel with unc-75 (unc, uncoordinated), the C. elegans homologue of the CELF͞BrunoL family protein that regulates mRNA alternative splicing and processing, and is also required specifically for synaptic transmission. We propose that neuronal SYD-9 proteins are previously uncharacterized and specific posttranscriptional regulators of synaptic vesicle endocytosis.BrunoL͞UNC-75 ͉ Caenorhabditis elegans ͉ endocytosis ͉ synaptic function C hemical synapses mediate neuronal communication through the regulated release of neurotransmitters from synaptic vesicles. Extensive studies have focused on the molecular machinery that mediates and regulates exocytosis, the process in which membrane fusion between synaptic vesicles and the plasma membrane leads to neurotransmitter release and endocytosis, the process that recovers synaptic vesicles from the plasma membrane (1, 2).The release of neurotransmitters is stimulated by the influx of Ca 2ϩ at the presynaptic active zones. Protein components of the vesicle membranes (synaptobrevin, SNB) and plasma membranes [syntaxin and SNAP-25 (synaptosome-associated protein of 25 kDa)] form a SNARE complex that functions as a minimal fusion machine to drive vesicle fusion (3-5). The formation and conformational change of the SNARE complex requires modulation by other proteins (6-9). Synaptotagmin (SNT) is a vesicle membrane protein that binds to Ca 2ϩ and forms complexes with phospholipids and SNARE complexes. It is a proposed Ca 2ϩ sensor for Ca 2ϩ -dependent exocytosis (10-12). SNT-1 knockout mice display selective loss of Ca 2ϩ -triggered fast exocytosis, and loss of SNT function in Caenorhabditis elegans and Drosophila leads to a large reduction of exocytosis (13,14). Disrupting the function of UNC13͞mUNC13 and UNC-18͞mUNC18 (UNC, uncoordinated) also leads to a reduction...

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A post-docking role for active zone protein Rim

Cited by 302 publications

References 41 publications

GABA Is Dispensable for the Formation of Junctional GABA Receptor Clusters inCaenorhabditis elegans

GABA Is Dispensable for the Formation of Junctional GABA Receptor Clusters inCaenorhabditis elegans

Mechanisms of Exocytosis in Insulin‐Secreting B‐Cells and Glucagon‐Secreting A‐Cells

The C2H2 zinc-finger protein SYD-9 is a putative posttranscriptional regulator for synaptic transmission

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