Isolation and Preliminary Biological Assessment of AADGAPLIRFamide and SVPGVLRFamide from Caenorhabditis elegans

Marks, Nicola; Shaw, Christopher; Halton, D W; Thompson, David P.; Geary, Timothy G.; Li, C.; Maule, Aaron G.

doi:10.1006/bbrc.2001.5524

Cited by 31 publications

(25 citation statements)

References 26 publications

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“…We could not further investigate the extent to which the differentiation of the VD MNs was affected in alr-1 mutants, owing to the lack of additional VD-or DD-specific markers. The flp-13 gene is predicted to encode at least six FMRFamiderelated neuropeptides (Li et al, 1999), two of which have been biochemically isolated from C. elegans (Li et al, 1999;Marks et al, 2001). Peptides encoded by flp-13 have been shown to cause a dramatic inhibition of locomotory behavior and paralysis when injected into Ascaris suum, and inhibit pharyngeal activity in C. elegans (Marks et al, 2001;Rogers et al, 2001), suggesting that these neuropeptides may act to modulate the inhibitory functions of GABA at the neuromuscular junction.…”

Section: Discussionmentioning

confidence: 99%

Regulation of chemosensory and GABAergic motor neuron development by theC. elegans Aristaless/Arxhomologalr-1

Melkman

Sengupta

2005

Development

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Mutations in the highly conserved Aristaless-related homeodomain protein ARX have been shown to underlie multiple forms of X-linked mental retardation. Arx knockout mice exhibit thinner cerebral cortices because of decreased neural precursor proliferation, and also exhibit defects in the differentiation and migration of GABAergic interneurons. However, the role of ARX in the observed behavioral and developmental abnormalities is unclear. The regulatory functions of individual homeodomain proteins and the networks in which they act are frequently highly conserved across species, although these networks may be deployed in different developmental contexts. In Drosophila, aristaless mutants exhibit defects in the development of terminal appendages, and Aristaless has been shown to function with the LIM-homeodomain protein LIM1 to regulate leg development. Here, we describe the role of the Aristaless/Arx homolog alr-1 in C. elegans. We show that alr-1 acts in a pathway with the LIM1 ortholog lin-11 to regulate the development of a subset of chemosensory neurons. Moreover, we demonstrate that the differentiation of a GABAergic motoneuron subtype is affected in alr-1 mutants, suggesting parallels with ARX functions in vertebrates. Investigating ALR-1 functions in C. elegans may yield insights into the role of this important protein in neuronal development and the etiology of mental retardation.

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Section: Discussionmentioning

confidence: 99%

Regulation of chemosensory and GABAergic motor neuron development by theC. elegans Aristaless/Arxhomologalr-1

Melkman

Sengupta

2005

Development

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“…3,[26][27][28] Recently, SYFDEKKSVPGVLRF-NH 2 was isolated 3,27 and EMPGVLRF-NH 2 was both predicted and isolated 3,27 ; neither was included in the current study. When we tested KSVPGVLRF-NH 2 (a predicted sequence 25 ) and SVPGVLRF-NH 2 (the isolated peptide [26][27][28] ), both peptides were equally potent to activate FLP-18R1b but SVPGVLRF-NH 2 was two fold more potent at the FLP-18R1a receptor (Table I). It is interesting to note that the shorter peptides were more potent than longer peptides and that the most potent was not a C. elegans but an A. suum peptide, AVPGVLRF-NH 2 (EC 50 7.6-13.1 nM).…”

Section: Elegans Gpcr Y58g8a4 Is a Flp-18 Receptor 345mentioning

confidence: 99%

FMRFamide‐like peptides encoded on the flp‐18 precursor gene activate two isoforms of the orphan Caenorhabditis elegans G‐protein‐coupled receptor Y58G8A.4 heterologously expressed in mammalian cells

Kubiak¹,

Larsen²,

Bowman³

et al. 2008

Biopolymers

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“…Many neuropeptides and neuropeptide receptors are known to influence muscle and neuronal activity and ultimately locomotion in C. elegans and other nematodes (Marks et al 2001;Rogers et al 2001;Keating et al 2003;Husson et al 2007). It is possible that one or more neuromodulators required to regulate locomotion are released from neuronal DCVs in wild-type animals but are not transported properly through the neuronal secretory pathway in unc-73 RhoGEF-2 or rab-2 mutants and not properly released from unc-31 mutant neurons.…”

Section: Unc-73 Rhogef-2 Isoforms and Neuromodulatory Protein Signalingmentioning

confidence: 99%

UNC-73/Trio RhoGEF-2 Activity Modulates Caenorhabditis elegans Motility Through Changes in Neurotransmitter Signaling Upstream of the GSA-1/Gαs Pathway

Pawson

Steven

2011

Genetics

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Rho-family GTPases play regulatory roles in many fundamental cellular processes. Caenorhabditis elegans UNC-73 RhoGEF isoforms function in axon guidance, cell migration, muscle arm extension, phagocytosis, and neurotransmission by activating either Rac or Rho GTPase subfamilies. Multiple differentially expressed UNC-73 isoforms contain a Rac-specific RhoGEF-1 domain, a Rho-specific RhoGEF-2 domain, or both domains. The UNC-73E RhoGEF-2 isoform is activated by the G-protein subunit Ga q and is required for normal rates of locomotion; however, mechanisms of UNC-73 and Rho pathway regulation of locomotion are not clear. To better define UNC-73 function in the regulation of motility we used cell-specific and inducible promoters to examine the temporal and spatial requirements of UNC-73 RhoGEF-2 isoform function in mutant rescue experiments. We found that UNC-73E acts within peptidergic neurons of mature animals to regulate locomotion rate. Although unc-73 RhoGEF-2 mutants have grossly normal synaptic morphology and weak resistance to the acetylcholinesterase inhibitor aldicarb, they are significantly hypersensitive to the acetylcholine receptor agonist levamisole, indicating alterations in acetylcholine neurotransmitter signaling. Consistent with peptidergic neuron function, unc-73 RhoGEF-2 mutants exhibit a decreased level of neuropeptide release from motor neuron dense core vesicles (DCVs). The unc-73 locomotory phenotype is similar to those of rab-2 and unc-31, genes with distinct roles in the DCV-mediated secretory pathway. We observed that constitutively active Ga s pathway mutations, which compensate for DCV-mediated signaling defects, rescue unc-73 RhoGEF-2 and rab-2 lethargic movement phenotypes. Together, these data suggest UNC-73 RhoGEF-2 isoforms are required for proper neurotransmitter signaling and may function in the DCV-mediated neuromodulatory regulation of locomotion rate.

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Isolation and Preliminary Biological Assessment of AADGAPLIRFamide and SVPGVLRFamide from Caenorhabditis elegans

Cited by 31 publications

References 26 publications

Regulation of chemosensory and GABAergic motor neuron development by theC. elegans Aristaless/Arxhomologalr-1

Regulation of chemosensory and GABAergic motor neuron development by theC. elegans Aristaless/Arxhomologalr-1

FMRFamide‐like peptides encoded on the flp‐18 precursor gene activate two isoforms of the orphan Caenorhabditis elegans G‐protein‐coupled receptor Y58G8A.4 heterologously expressed in mammalian cells

UNC-73/Trio RhoGEF-2 Activity Modulates Caenorhabditis elegans Motility Through Changes in Neurotransmitter Signaling Upstream of the GSA-1/Gαs Pathway

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