The C. elegans unc-18 gene encodes a protein expressed in motor neurons

Gengyo-Ando, Keiko; Kamiya, Yushi; Yamakawa, Ayanori; Kodaira, Ken-Ichi; Nishiwaki, Kiyoji; Miwa, Johji; Hori, Isao; Hosono, Ryuji

doi:10.1016/0896-6273(93)90080-b

Cited by 109 publications

(72 citation statements)

References 28 publications

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“…In the unc-18 mutant, VenusTUNC-6 accumulated in muscle cells. This finding was unexpected, because UNC-18 belongs to the SM (Sec1/Munc18-like) protein family (Gengyo-Ando et al 1993;Malsam et al 2008; Sü dhof and Rothman 2009), which regulates vesicle exocytosis by interacting with syntaxin, a member of the SNARE proteins in neurons (Sassa et al 1999;Weimer et al 2003;Malsam et al 2008;Sü dhof and Rothman 2009). Indeed, UNC-18 is expressed in neurons but not in muscle (Gengyo-Ando et al 1993).…”

Section: Discussionmentioning

confidence: 98%

“…UNC-18, which is homologous to the SM (Sec1/Munc18-like) proteins, regulates a multistep vesicle exocytosis process in neurons, in cooperation with SNARE proteins (Gengyo-Ando et al 1993;Malsam et al 2008; Sü dhof and Rothman 2009). Therefore, we next examined whether neuronal UNC-18 regulates the localization of VenusTUNC-6 in muscle.…”

Section: Resultsmentioning

confidence: 99%

“…The unc-18 ORF was amplified from pPCR2.1F27D9#F1R1 (Gengyo-Ando et al 1993), and inserted into the mCherry (McNally et al 2006) expression vector pNW5 (myo-3 promoterTmCherry) or pNW19 (H20 promoterTmCherry), resulting in the myo-3pTunc-18TmCherry (pNW7) and H20pTunc-18TmCherry (pNW20) constructs.…”

Section: Mutations Usedmentioning

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: Discussionmentioning

confidence: 98%

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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“…Indeed, vesicle accumulation is observed in synaptic terminals of C. elegans unc-18 mutants (E. Jorgensen, E. Hartwieg, and H. R. Horvitz, unpublished data). UNC-18 is likely to be a component of the docking and/or fusion machinery (Gengyo-Ando et al, 1993;Pevsner, 1996), because vertebrate homologs interact directly with syntaxin, a component of the proposed synaptic machinery (Hata et al, 1993;Garcia et al, 1994;Pevsner et al, 1994).…”

Section: Discussionmentioning

confidence: 99%

Caenorhabditis elegans rab-3Mutant Synapses Exhibit Impaired Function and Are Partially Depleted of Vesicles

et al. 1997

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Rab molecules regulate vesicular trafficking in many different exocytic and endocytic transport pathways in eukaryotic cells. In neurons, rab3 has been proposed to play a crucial role in regulating synaptic vesicle release. To elucidate the role of rab3 in synaptic transmission, we isolated and characterized Caenorhabditis elegans rab-3 mutants. Similar to the mouse rab3A mutants, these mutants survived and exhibited only mild behavioral abnormalities. In contrast to the mouse mutants, synaptic transmission was perturbed in these animals. Extracellular electrophysiological recordings revealed that synaptic transmission in the pharyngeal nervous system was impaired. Furthermore, rab-3 animals were resistant to the acetylcholinesterase inhibitor aldicarb, suggesting that cholinergic transmission was generally depressed. Last, synaptic vesicle populations were redistributed in rab-3 mutants. In motor neurons, vesicle populations at synapses were depleted to 40% of normal levels, whereas in intersynaptic regions of the axon, vesicle populations were elevated. On the basis of the morphological defects at neuromuscular junctions, we postulate that RAB-3 may regulate recruitment of vesicles to the active zone or sequestration of vesicles near release sites.

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“…Continuant le parcours brillant initié dès le début de seś etudes doctorales, Novick a construit un corpus substantiel de travaux hautement originaux qui révèlent les mécanismes détaillés associésà la production, la migration et la fusion des vésicules de transportà la surface de la cellule de levure.Étant donné la conservation fondamentale des séquences du gène SEC, il n'est pas surprenant que les interprétations de Novick soient valables pour tous lesévènements comparables de ciblage/fusion de vésicules chez les métazoaires et les mammifères. Effectivement SEC1 aété reconnu comme apparenté au gène unc-18 isolé dans la collection originelle des mutants incoordonnés de C. elegans assemblée par Sydney Brenner (Brenner, 1974 ;Gengyo-Ando et al, 1993). Et l'on sait que la protéine Sec1 joue un rôle universel dans le contrôle de l'effet de la protéine SNARE sur la fusion des vésicules.…”

Section: Cloner Des Gènes Pour Compléter L'analyse Fonctionnelle Des unclassified

Les gènes et les protéines qui contrôlent la voie de sécrétion

Schekman

2015

Biologie Aujourd'hui

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The C. elegans unc-18 gene encodes a protein expressed in motor neurons

Cited by 109 publications

References 28 publications

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

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

Caenorhabditis elegans rab-3Mutant Synapses Exhibit Impaired Function and Are Partially Depleted of Vesicles

Les gènes et les protéines qui contrôlent la voie de sécrétion

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