Neuronal signaling modulates protein homeostasis in Caenorhabditis elegans post-synaptic muscle cells. Export

@article{citeulike:3336087, abstract = {Protein homeostasis maintains proper intracellular balance by promoting protein folding and clearance mechanisms while minimizing the stress caused by the accumulation of misfolded and damaged proteins. Chronic expression of aggregation-prone proteins is deleterious to the cell and has been linked to a wide range of conformational disorders. The molecular response to misfolded proteins is highly conserved and generally studied as a cell-autonomous process. Here, we provide evidence that neuronal signaling is an important modulator of protein homeostasis in post-synaptic muscle cells. In a forward genetic screen in Caenorhabditis elegans for enhancers of polyglutamine aggregation in muscle cells, we identified unc-30, a neuron-specific transcription factor that regulates the synthesis of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). We used additional sensors of protein conformational states to show that defective GABA signaling or increased acetylcholine (ACh) signaling causes a general imbalance in protein homeostasis in post-synaptic muscle cells. Moreover, exposure to GABA antagonists or ACh agonists has a similar effect, which reveals that toxins that act at the neuromuscular junction are potent modifiers of protein conformational disorders. These results demonstrate the importance of intercellular communication in intracellular homeostasis.}, author = {Garcia, S. M. and Casanueva, M. O. and Silva, M. C. and Amaral, M. D. and Morimoto, R. I.}, citeulike-article-id = {3336087}, citeulike-linkout-0 = {http://view.ncbi.nlm.nih.gov/pubmed/18006691}, citeulike-linkout-1 = {http://www.hubmed.org/display.cgi?uids=18006691}, citeulike-linkout-2 = {http://www.wormbase.org/db/misc/paper?name=WBPaper00031213}, journal = {Genes Dev}, keywords = {ace-1, ace-2, article, b056410, c46f111, c48a71, c\_elegans, caenorhabditis\_elegans, celegans, egl-19, elegans, f07a57, nematode, unc-15, unc-30, unc-52, unc-93, w09b121, wormbase, y44e3a2, zc1012}, pages = {3006--3016}, posted-at = {2008-09-25 14:55:03}, priority = {3}, title = {Neuronal signaling modulates protein homeostasis in Caenorhabditis elegans post-synaptic muscle cells.}, url = {http://view.ncbi.nlm.nih.gov/pubmed/18006691}, volume = {21}, year = {2007} }

TY - JOUR ID - citeulike:3336087 L3 - citeulike-article-id:3336087 N2 - Protein homeostasis maintains proper intracellular balance by promoting protein folding and clearance mechanisms while minimizing the stress caused by the accumulation of misfolded and damaged proteins. Chronic expression of aggregation-prone proteins is deleterious to the cell and has been linked to a wide range of conformational disorders. The molecular response to misfolded proteins is highly conserved and generally studied as a cell-autonomous process. Here, we provide evidence that neuronal signaling is an important modulator of protein homeostasis in post-synaptic muscle cells. In a forward genetic screen in Caenorhabditis elegans for enhancers of polyglutamine aggregation in muscle cells, we identified unc-30, a neuron-specific transcription factor that regulates the synthesis of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). We used additional sensors of protein conformational states to show that defective GABA signaling or increased acetylcholine (ACh) signaling causes a general imbalance in protein homeostasis in post-synaptic muscle cells. Moreover, exposure to GABA antagonists or ACh agonists has a similar effect, which reveals that toxins that act at the neuromuscular junction are potent modifiers of protein conformational disorders. These results demonstrate the importance of intercellular communication in intracellular homeostasis. JF - Genes Dev EP - 3016 TI - Neuronal signaling modulates protein homeostasis in Caenorhabditis elegans post-synaptic muscle cells. VL - 21 SP - 3006 KW - ace-1 KW - ace-2 KW - article KW - b056410 KW - c46f111 KW - c48a71 KW - c_elegans KW - caenorhabditis_elegans KW - celegans KW - egl-19 KW - elegans KW - f07a57 KW - nematode KW - unc-15 KW - unc-30 KW - unc-52 KW - unc-93 KW - w09b121 KW - wormbase KW - y44e3a2 KW - zc1012 AU - Garcia, SM AU - Casanueva, MO AU - Silva, MC AU - Amaral, MD AU - Morimoto, RI PY - 2007/// UR - http://view.ncbi.nlm.nih.gov/pubmed/18006691 ER -