unc-68 encodes a ryanodine receptor involved in regulating C. elegans body-wall muscle contraction.

Maryon, Edward B.; Coronado, Roberto; Anderson, Philip

doi:10.1083/jcb.134.4.885

Cited by 135 publications

(146 citation statements)

References 49 publications

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“…The reference alleles unc-68(e540) and unc-68(r1162) exhibited the same phenotype ( Figure 3B). UNC-68 is homologous to ryanodine receptors (RyRs), which regulate body-wall muscle contraction by controlling Ca 21 release from the endoplasmic reticulum (ER) (Maryon et al 1996;Sakube et al 1997;Zalk et al 2007). This release of Ca 21 mediated by UNC-68 is also required for regulating both spontaneous and evoked neurotransmitter release (Liu et al 2005).…”

Section: Resultsmentioning

confidence: 99%

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Genes Required for Cellular UNC-6/Netrin Localization in Caenorhabditis elegans

et al. 2010

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UNC-6/Netrin is an evolutionarily conserved, secretory axon guidance molecule. In Caenorhabditis elegans, UNC-6 provides positional information to the axons of developing neurons, probably by establishing a concentration gradient from the ventral to the dorsal side of the animal. Although the proper localization of UNC-6 is important for accurate neuronal network formation, little is known about how its localization is regulated. Here, to examine the localization mechanism for UNC-6, we generated C. elegans expressing UNC-6 tagged with the fluorescent protein Venus and identified 13 genes, which are involved in the cellular localization of VenusTUNC-6. For example, in unc-51, unc-14, and unc-104 mutants, the neurons showed an abnormal accumulation of VenusTUNC-6 in the cell body and less than normal level of VenusTUNC-6 in the axon. An aberrant accumulation of VenusTUNC-6 in muscle cells was seen in unc-18 and unc-68 mutants. unc-51, unc-14, and unc-104 mutants also showed defects in the guidance of dorso-ventral axons, suggesting that the abnormal localization of UNC-6 disturbed the positional information it provides. We propose that these genes regulate the process of UNC-6 secretion: expression, maturation, sorting, transport, or exocytosis. Our findings provide novel insight into the localization mechanism of the axon guidance molecule UNC-6/ Netrin.

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Section: Resultsmentioning

confidence: 99%

“…UNC-68 is homologous to ryanodine receptors (RyRs), a class of Ca 21 channels (Maryon et al 1996;Sakube et al 1997;Zalk et al 2007). UNC-68 plays important roles in muscle contraction, mediating Ca 21 -induced Ca 21 release (CICR) from the endoplasmic reticulum (ER).…”

Section: Discussionmentioning

confidence: 99%

Genes Required for Cellular UNC-6/Netrin Localization in Caenorhabditis elegans

et al. 2010

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“…In nonmammalian vertebrates RyRa and RyRb are highly homologous to the three mammalian isoforms (Oyamada et al 1994;Ottini et al 1996). RyRs have been identified in Drosophila (D) melanigaster, Caenorhabditis (C) elegans, and Homarus americanus Maryon et al 1996;Quinn et al 1998). The three mammalian isoforms are 65% identical in sequence (Hakamata et al 1992) with three major regions of diversity: D1, between residues 4254 and 4631 in skeletal sequence and 4210 and 4562 in cardiac sequence; D2 between residues 1342 and 1403 in skeletal sequence and residues 1353 and 1397 in the cardiac sequence; D3, between residues 1872 and 1923 in skeletal sequence and 1852 and 1890 in the cardiac sequence.…”

Section: Ryanodine Receptor Genes and Isoformsmentioning

confidence: 99%

Ryanodine Receptors: Structure, Expression, Molecular Details, and Function in Calcium Release

Lanner¹,

Georgiou²,

Joshi³

et al. 2010

Cold Spring Harbor Perspectives in Biology

648

572

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Ryanodine receptors (RyRs) are located in the sarcoplasmic/endoplasmic reticulum membrane and are responsible for the release of Ca 2þ from intracellular stores during excitation-contraction coupling in both cardiac and skeletal muscle. RyRs are the largest known ion channels (.2MDa) and exist as three mammalian isoforms (RyR 1 -3), all of which are homotetrameric proteins that interact with and are regulated by phosphorylation, redox modifications, and a variety of small proteins and ions. Most RyR channel modulators interact with the large cytoplasmic domain whereas the carboxy-terminal portion of the protein forms the ion-conducting pore. Mutations in RyR2 are associated with human disorders such as catecholaminergic polymorphic ventricular tachycardia whereas mutations in RyR1 underlie diseases such as central core disease and malignant hyperthermia. This chapter examines the current concepts of the structure, function and regulation of RyRs and assesses the current state of understanding of their roles in associated disorders.

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“…Loss-of-function; putative null (Maryon et al 1996) unc-68(r1162) 3.7 Kb deletion, removing about half of the coding sequence and all transmembrane domains…”

Section: Strain Name Genotypementioning

confidence: 99%

“…Loss-of-function; putative null (Maryon et al 1996) Plasmids DNA Name Used StrataScript Reverse Transcriptase and a primer engineered with a restriction site to amplify the full length ida-1 cDNA minus its stop codon (~2.3 Kb) from C. elegans mRNA. The 3' primer is engineered such that the native stop codon of ida-1 is eliminated and replaced with a 2 nucleotide frame adjusting spacer followed by the Age I site that allows inframe insertion of an Age I/ Spe I 3-intron GFP and unc-54 3' end.…”

Section: Strain Name Genotypementioning

confidence: 99%

A Novel CaM Kinase II Pathway Controls the Location of Neuropeptide Release fromCaenorhabditis elegansMotor Neurons

Hoover

Edwards

et al. 2014

Genetics

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Neurons release neuropeptides via the regulated exocytosis of dense core vesicles (DCVs) to evoke or modulate behaviors. We found that Caenorhabditis elegans motor neurons send most of their DCVs to axons, leaving very few in the cell somas. How neurons maintain this skewed distribution and the extent to which it can be altered to control DCV numbers in axons or to drive release from somas for different behavioral impacts is unknown. Using a forward genetic screen, we identified loss-of-function mutations in UNC-43 (CaM kinase II) that reduce axonal DCV levels by 90% and cell soma/dendrite DCV levels by 80%, leaving small synaptic vesicles largely unaffected. Blocking regulated secretion in unc-43 mutants restored near wild-type axonal levels of DCVs. Time-lapse video microscopy showed no role for CaM kinase II in the transport of DCVs from cell somas to axons. In vivo secretion assays revealed that much of the missing neuropeptide in unc-43 mutants is secreted via a regulated secretory pathway requiring UNC-31 (CAPS) and . DCV cargo levels in unc-43 mutants are similarly low in cell somas and the axon initial segment, indicating that the secretion occurs prior to axonal transport. Genetic pathway analysis suggests that abnormal neuropeptide function contributes to the sluggish basal locomotion rate of unc-43 mutants. These results reveal a novel pathway controlling the location of DCV exocytosis and describe a major new function for CaM kinase II. BOTH neurons and neuroendocrine cells rely on the controlled release of neuropeptides via dense core vesicle (DCV) exocytosis to evoke or modulate behaviors (Scheller and Axel 1984;Kupfermann 1991;T. Liu et al. 2007;Li and Kim 2008). The DCVs in neuroendocrine and PC12 cells are much more abundant and accessible to biochemical and physiological experiments than those in neurons. For example, in chromaffin and pancreatic b-cells (both neuroendocrine cells), DCVs can number in the tens of thousands per cell and can occupy 31 and 12% of the cell volume, respectively (Dean 1973;Plattner et al. 1997). Exploiting these advantages, studies in PC12 and neuroendocrine cells have revealed that DCVs arise from a regulated secretory pathway. The pathway begins in the trans Golgi, where various sorting mechanisms cause regulated secretory proteins, such as neuropeptides and their processing enzymes, to coalesce into vesicles that bud from the trans Golgi to form immature DCVs. Additional sorting of non-DCV cargos away from DCV cargos occurs as DCVs mature through this pathway (Arvan and Castle 1998;Tooze et al. 2001;Borgonovo et al. 2006).DCVs must selectively retain and protect several distinct cargos that have different physical states as they mature. These include the neuropeptide core, which is thought to be in an aggregated state, the neuropeptide-processing enzymes PC-2 convertase and carboxypeptidase E, possibly soluble cargos, and transmembrane cargos.While neurons and neuroendocrine cells share this core pathway for DCV production, neurons have evolved additional...

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unc-68 encodes a ryanodine receptor involved in regulating C. elegans body-wall muscle contraction.

Cited by 135 publications

References 49 publications

Genes Required for Cellular UNC-6/Netrin Localization in Caenorhabditis elegans

Genes Required for Cellular UNC-6/Netrin Localization in Caenorhabditis elegans

Ryanodine Receptors: Structure, Expression, Molecular Details, and Function in Calcium Release

A Novel CaM Kinase II Pathway Controls the Location of Neuropeptide Release fromCaenorhabditis elegansMotor Neurons

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