Abstract | BACKGROUND: METHODOLOGY/PRINCIPAL FINDINGS: We 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/SIGNIFICANCE: Our 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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Authors | Mary Wiese, Adam Antebi, Hui Zheng |
Journal | PloS one
(PLoS One)
Vol. 5
Issue 9
(Sep 20 2010)
ISSN: 1932-6203 [Electronic] United States |
PMID | 20862215
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- APL-1 protein, C elegans
- Caenorhabditis elegans Proteins
- Membrane Proteins
- Monomeric GTP-Binding Proteins
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Topics |
- Alzheimer Disease
(genetics, metabolism)
- Amino Acid Motifs
- Animals
- Caenorhabditis elegans
(chemistry, genetics, growth & development, metabolism)
- Caenorhabditis elegans Proteins
(chemistry, genetics, metabolism)
- Cell Membrane
(chemistry, genetics, metabolism)
- Disease Models, Animal
- Endosomes
(chemistry, genetics, metabolism)
- Humans
- Membrane Proteins
(chemistry, genetics, metabolism)
- Molting
- Monomeric GTP-Binding Proteins
(genetics, metabolism)
- Neurons
(metabolism)
- Protein Transport
- Synapses
(chemistry, genetics, metabolism)
- Synaptic Transmission
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