FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W1509721882> ?p ?o ?g. }

• W1509721882 endingPage "33728" @default.
• W1509721882 startingPage "33719" @default.
• W1509721882 abstract "Emerging evidence from studies of Huntington disease (HD) pathophysiology suggests that huntingtin (htt) and its associated protein HAP1 participate in intracellular trafficking and synaptic function. However, it is largely unknown whether AMPA receptor trafficking, which is crucial for controlling the efficacy of synaptic excitation, is affected by the mutant huntingtin with polyglutamine expansion (polyQ-htt). In this study, we found that expressing polyQ-htt in neuronal cultures significantly decreased the amplitude and frequency of AMPAR-mediated miniature excitatory postsynaptic current (mEPSC), while expressing wild-type huntingtin (WT-htt) increased mEPSC. AMPAR-mediated synaptic transmission was also impaired in a transgenic mouse model of HD expressing polyQ-htt. The effect of polyQ-htt on mEPSC was mimicked by knockdown of HAP1 and occluded by the dominant negative HAP1. Moreover, we found that huntingtin affected mESPC via a mechanism depending on the kinesin motor protein, KIF5, which controls the transport of GluR2-containing AMPARs along microtubules in dendrites. The GluR2/KIF5/HAP1 complex was disrupted and dissociated from microtubules in the HD mouse model. Together, these data suggest that AMPAR trafficking and function is impaired by mutant huntingtin, presumably due to the interference of KIF5-mediated microtubule-based transport of AMPA receptors. The diminished strength of glutamatergic transmission could contribute to the deficits in movement control and cognitive processes in HD conditions. Emerging evidence from studies of Huntington disease (HD) pathophysiology suggests that huntingtin (htt) and its associated protein HAP1 participate in intracellular trafficking and synaptic function. However, it is largely unknown whether AMPA receptor trafficking, which is crucial for controlling the efficacy of synaptic excitation, is affected by the mutant huntingtin with polyglutamine expansion (polyQ-htt). In this study, we found that expressing polyQ-htt in neuronal cultures significantly decreased the amplitude and frequency of AMPAR-mediated miniature excitatory postsynaptic current (mEPSC), while expressing wild-type huntingtin (WT-htt) increased mEPSC. AMPAR-mediated synaptic transmission was also impaired in a transgenic mouse model of HD expressing polyQ-htt. The effect of polyQ-htt on mEPSC was mimicked by knockdown of HAP1 and occluded by the dominant negative HAP1. Moreover, we found that huntingtin affected mESPC via a mechanism depending on the kinesin motor protein, KIF5, which controls the transport of GluR2-containing AMPARs along microtubules in dendrites. The GluR2/KIF5/HAP1 complex was disrupted and dissociated from microtubules in the HD mouse model. Together, these data suggest that AMPAR trafficking and function is impaired by mutant huntingtin, presumably due to the interference of KIF5-mediated microtubule-based transport of AMPA receptors. The diminished strength of glutamatergic transmission could contribute to the deficits in movement control and cognitive processes in HD conditions." @default.
• W1509721882 created "2016-06-24" @default.
• W1509721882 creator A5003928093 @default.
• W1509721882 creator A5009240555 @default.
• W1509721882 creator A5014852707 @default.
• W1509721882 creator A5019954627 @default.
• W1509721882 creator A5021915616 @default.
• W1509721882 creator A5036408954 @default.
• W1509721882 creator A5041062049 @default.
• W1509721882 creator A5055056437 @default.
• W1509721882 creator A5072263969 @default.
• W1509721882 creator A5075408897 @default.
• W1509721882 creator A5076452990 @default.
• W1509721882 creator A5084685500 @default.
• W1509721882 date "2011-09-01" @default.
• W1509721882 modified "2023-09-29" @default.
• W1509721882 title "Impaired α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) Receptor Trafficking and Function by Mutant Huntingtin" @default.
• W1509721882 cites W1509279614 @default.
• W1509721882 cites W1605454745 @default.
• W1509721882 cites W1616958874 @default.
• W1509721882 cites W1970765799 @default.
• W1509721882 cites W1972764647 @default.
• W1509721882 cites W1976175605 @default.
• W1509721882 cites W1977569817 @default.
• W1509721882 cites W1978104052 @default.
• W1509721882 cites W1982623268 @default.
• W1509721882 cites W1983511812 @default.
• W1509721882 cites W1990567359 @default.
• W1509721882 cites W1994875311 @default.
• W1509721882 cites W1995167983 @default.
• W1509721882 cites W1995847434 @default.
• W1509721882 cites W1996592124 @default.
• W1509721882 cites W1996990492 @default.
• W1509721882 cites W1998237974 @default.
• W1509721882 cites W2000971037 @default.
• W1509721882 cites W2006472192 @default.
• W1509721882 cites W2012887006 @default.
• W1509721882 cites W2018891368 @default.
• W1509721882 cites W2030258195 @default.
• W1509721882 cites W2034823208 @default.
• W1509721882 cites W2040683034 @default.
• W1509721882 cites W2041119962 @default.
• W1509721882 cites W2042567578 @default.
• W1509721882 cites W2048320127 @default.
• W1509721882 cites W2051634852 @default.
• W1509721882 cites W2052970339 @default.
• W1509721882 cites W2052999972 @default.
• W1509721882 cites W2053626372 @default.
• W1509721882 cites W2062682951 @default.
• W1509721882 cites W2085266650 @default.
• W1509721882 cites W2091323369 @default.
• W1509721882 cites W2094784470 @default.
• W1509721882 cites W2095099413 @default.
• W1509721882 cites W2101286436 @default.
• W1509721882 cites W2110715131 @default.
• W1509721882 cites W2112001810 @default.
• W1509721882 cites W2113547127 @default.
• W1509721882 cites W2125224248 @default.
• W1509721882 cites W2128574573 @default.
• W1509721882 cites W2129765787 @default.
• W1509721882 cites W2132164151 @default.
• W1509721882 cites W2134022293 @default.
• W1509721882 cites W2135783352 @default.
• W1509721882 cites W2142716581 @default.
• W1509721882 cites W2143116460 @default.
• W1509721882 cites W2145510016 @default.
• W1509721882 cites W2150852495 @default.
• W1509721882 cites W2155924717 @default.
• W1509721882 cites W2159269805 @default.
• W1509721882 cites W2168029064 @default.
• W1509721882 doi "https://doi.org/10.1074/jbc.m111.236521" @default.
• W1509721882 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3190808" @default.
• W1509721882 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/21832090" @default.
• W1509721882 hasPublicationYear "2011" @default.
• W1509721882 type Work @default.
• W1509721882 sameAs 1509721882 @default.
• W1509721882 citedByCount "47" @default.
• W1509721882 countsByYear W15097218822012 @default.
• W1509721882 countsByYear W15097218822013 @default.
• W1509721882 countsByYear W15097218822014 @default.
• W1509721882 countsByYear W15097218822015 @default.
• W1509721882 countsByYear W15097218822016 @default.
• W1509721882 countsByYear W15097218822017 @default.
• W1509721882 countsByYear W15097218822018 @default.
• W1509721882 countsByYear W15097218822019 @default.
• W1509721882 countsByYear W15097218822020 @default.
• W1509721882 countsByYear W15097218822021 @default.
• W1509721882 countsByYear W15097218822022 @default.
• W1509721882 countsByYear W15097218822023 @default.
• W1509721882 crossrefType "journal-article" @default.
• W1509721882 hasAuthorship W1509721882A5003928093 @default.
• W1509721882 hasAuthorship W1509721882A5009240555 @default.
• W1509721882 hasAuthorship W1509721882A5014852707 @default.
• W1509721882 hasAuthorship W1509721882A5019954627 @default.
• W1509721882 hasAuthorship W1509721882A5021915616 @default.
• W1509721882 hasAuthorship W1509721882A5036408954 @default.
• W1509721882 hasAuthorship W1509721882A5041062049 @default.
• W1509721882 hasAuthorship W1509721882A5055056437 @default.

• next