Comparison of two Caenorhabditis genes encoding FMRFamide(Phe-Met-Arg-Phe-NH2)-like peptides

Schinkmann, K.; Li, C.

doi:10.1016/0169-328x(94)90137-6

Cited by 24 publications

(12 citation statements)

References 34 publications

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“…We suspect that APL-1 accumulation in unc-108(n3263) mutants may be due to incorrect sorting of APL-1 into the proper vesicular population upstream of anterograde transport. It is still unknown whether APL-1 is present in dense core vesicles, although this subset of vesicles is primarily transported by UNC-104 [56], which also appears to be the transporter most involved in proper localization and expression levels of APL-1 (Figure 4). Since the localization of APL-1 is dependent upon the presence of functional UNC-108, and the two proteins colocalize, it is possible that APL-1 may play a role either within the DCVs, or actively operating with UNC-108 in the maturation of DCVs.…”

Section: Discussionmentioning

confidence: 99%

Intracellular Trafficking and Synaptic Function of APL-1 in Caenorhabditis elegans

2010

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BackgroundAlzheimer's disease (AD) is a neurodegenerative disorder primarily characterized by the deposition of β-amyloid plaques in the brain. Plaques are composed of the amyloid-β peptide derived from cleavage of the amyloid precursor protein (APP). Mutations in APP lead to the development of Familial Alzheimer's Disease (FAD), however, the normal function of this protein has proven elusive. The organism Caenorhabditis elegans is an attractive model as the amyloid precursor-like protein (APL-1) is the single ortholog of APP, and loss of apl-1 leads to a severe molting defect and early larval lethality.Methodology/Principal FindingsWe report here that lethality and molting can be rescued by full length APL-1, C-terminal mutations as well as a C-terminal truncation, suggesting that the extracellular region of the protein is essential for viability. RNAi knock-down of apl-1 followed by drug testing on the acetylcholinesterase inhibitor aldicarb showed that loss of apl-1 leads to aldicarb hypersensitivity, indicating a defect in synaptic function. The aldicarb hypersensitivity can be rescued by full length APL-1 in a dose dependent fashion. At the cellular level, kinesins UNC-104/KIF-1A and UNC-116/kinesin-1 are positive regulators of APL-1 expression in the neurons. Knock-down of the small GTPase rab-5 also leads to a dramatic decrease in the amount of apl-1 expression in neurons, suggesting that trafficking from the plasma membrane to the early endosome is important for apl-1 function. Loss of function of a different small GTPase, UNC-108, on the contrary, leads to the retention of APL-1 in the cell body.Conclusions/SignificanceOur results reveal novel insights into the intracellular trafficking of APL-1 and we report a functional role for APL-1 in synaptic transmission.

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Section: Discussionmentioning

confidence: 99%

Intracellular Trafficking and Synaptic Function of APL-1 in Caenorhabditis elegans

2010

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“…In nematodes, the flp-1 gene encodes 7 FMRFa-related neuropeptides. Analysis of that gene in two related species revealed several evolutionarily conserved sequences within intronic regions (Schinkman and Li, 1995). Comparable transcriptional analysis may reveal whether this pattern of regulatory organization is a conserved feature between distantly related FMRFa genes.…”

Section: Cell Type-specific Transcriptional Regulationmentioning

confidence: 95%

Cell type-specific regulatory sequences control expression of theDrosophila FMRF-NH2 neuropeptide gene

Benveniste

Taghert

1999

J. Neurobiol.

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The FMRFamide (dFMRFa) neuropeptide gene is expressed in about 17 diverse cell types in the Drosophila central nervous system. This expression pattern is generated by transcriptional control elements that are distributed over 8 kilobases of dFMRFa DNA. Previous studies identified one enhancer within the dFMRFa 5′ region that is both necessary and sufficient to drive reporter transgene expression in one of the 17 dFMRFa cell types, the OL2 neurons. We now report the presence of two additional, non‐overlapping enhancers within the gene: One drives expression by the six Tv neuroendocrine cells, and another in the four X and X2 interneurons. We also show that the Tv neuron‐specific enhancer itself has complex organization, with several positively and negatively acting cis elements. Together, these results describe the organization of what is likely to be a prototypic neuronal gene promoter: an assemblage of multiple, independent, cell type–specific enhancers, each consisting of multiple quantitative elements. © 1999 John Wiley & Sons, Inc. J Neurobiol 38: 507–520, 1999

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“…Moreover, as the genes for neuropeptides are cloned, it is becoming apparent that some peptide families consist of large numbers of related peptides (e.g., Miller et al 1993a,b;Santama et al 1995;Kellett et al 1994;Schinkmann and Li 1994;Schneider et al 1993), many of which may be labeled by a single antiserum. Therefore, for any of the peptide immunoreactivities studied here, it is not clear how many different, related peptides are present in any of the labelled structures.…”

Section: Colocalization Of Modulators In Individual Profilesmentioning

confidence: 99%

Organization of the stomatogastric neuropil of the crab, Cancer borealis, as revealed by modulator immunocytochemistry

Christie

Baldwin

Marder

et al. 1997

Cell and Tissue Research

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We used antibodies to a number of neuromodulatory substances, including serotonin, FLRF amide, red pigment-concentrating hormone, substance P, proctolin and cholecystokinin, to investigate the distribution of molecules similar to these substances in the stomatogastric ganglion of the crab, Cancer borealis. No immunoreactivity was seen in the region of the cell bodies that surrounds the neuropil and little was found in the core of the neuropil (where the primary neurites of the intrinsic neurons occupy most of the space). Instead, modulator immunolabel was densely packed in the more peripheral portion of the neuropil that surrounded the core. Within this peripheral neuropil, profiles appeared quite uniformly distributed. Double-labeling showed that there were limited differences in distribution between the labels examined in our study. The only immunolabeled structures that showed a distinct differential distribution within the stomatogastric neuropil were a population of >/=10 microm varicosities that arose from a pair of input fibers that we termed the large varicosity fibers. These varicosities were immunolabelled by antisera for three different peptides. Taken collectively, these data shows that there is a stereotyped distribution of modulator immunoreactivity within the crab stomatogastric neuropil. However, this segregation is more rudimentary than that reported for the intrinsic stomatogastric neurons.

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Comparison of two Caenorhabditis genes encoding FMRFamide(Phe-Met-Arg-Phe-NH2)-like peptides

Cited by 24 publications

References 34 publications

Intracellular Trafficking and Synaptic Function of APL-1 in Caenorhabditis elegans

Intracellular Trafficking and Synaptic Function of APL-1 in Caenorhabditis elegans

Cell type-specific regulatory sequences control expression of theDrosophila FMRF-NH2 neuropeptide gene

Organization of the stomatogastric neuropil of the crab, Cancer borealis, as revealed by modulator immunocytochemistry

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