Davis_2010_Mol.Cell.Neurosci_44_307

Reference

Title : Regulated lysosomal trafficking as a mechanism for regulating GABAA receptor abundance at synapses in Caenorhabditis elegans - Davis_2010_Mol.Cell.Neurosci_44_307
Author(s) : Davis KM , Sturt BL , Friedmann AJ , Richmond JE , Bessereau JL , Grant BD , Bamber BA
Ref : Molecular & Cellular Neurosciences , 44 :307 , 2010
Abstract :

GABA(A) receptor plasticity is important for both normal brain function and disease progression. We are studying GABA(A) receptor plasticity in Caenorhabditis elegans using a genetic approach. Acute exposure of worms to the GABA(A) agonist muscimol hyperpolarizes postsynaptic cells, causing paralysis. Worms adapt after several hours, but show uncoordinated locomotion consistent with decreased GABA signaling. Using patch-clamp and immunofluorescence approaches, we show that GABA(A) receptors are selectively removed from synapses during adaptation. Subunit mRNA levels were unchanged, suggesting a post-transcriptional mechanism. Mutants with defective lysosome function (cup-5) show elevated GABA(A) receptor levels at synapses prior to muscimol exposure. During adaptation, these receptors are removed more slowly, and accumulate in intracellular organelles positive for the late endosome marker GFP-RAB-7. These findings suggest that chronic agonist exposure increases endocytosis and lysosomal trafficking of GABA(A) receptors, leading to reduced levels of synaptic GABA(A) receptors and reduced postsynaptic GABA sensitivity.

PubMedSearch : Davis_2010_Mol.Cell.Neurosci_44_307
PubMedID: 20403442

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Citations formats

Davis KM, Sturt BL, Friedmann AJ, Richmond JE, Bessereau JL, Grant BD, Bamber BA (2010)
Regulated lysosomal trafficking as a mechanism for regulating GABAA receptor abundance at synapses in Caenorhabditis elegans
Molecular & Cellular Neurosciences 44 :307

Davis KM, Sturt BL, Friedmann AJ, Richmond JE, Bessereau JL, Grant BD, Bamber BA (2010)
Molecular & Cellular Neurosciences 44 :307