FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2072856670> ?p ?o ?g. }

• W2072856670 endingPage "28682" @default.
• W2072856670 startingPage "28674" @default.
• W2072856670 abstract "Despite great functional diversity, characterization of the α/β-hydrolase fold proteins that encompass a superfamily of hydrolases, heterophilic adhesion proteins, and chaperone domains reveals a common structural motif. By incorporating the R451C mutation found in neuroligin (NLGN) and associated with autism and the thyroglobulin G2320R (G221R in NLGN) mutation responsible for congenital hypothyroidism into NLGN3, we show that mutations in the α/β-hydrolase fold domain influence folding and biosynthetic processing of neuroligin3 as determined by in vitro susceptibility to proteases, glycosylation processing, turnover, and processing rates. We also show altered interactions of the mutant proteins with chaperones in the endoplasmic reticulum and arrest of transport along the secretory pathway with diversion to the proteasome. Time-controlled expression of a fluorescently tagged neuroligin in hippocampal neurons shows that these mutations compromise neuronal trafficking of the protein, with the R451C mutation reducing and the G221R mutation virtually abolishing the export of NLGN3 from the soma to the dendritic spines. Although the R451C mutation causes a local folding defect, the G221R mutation appears responsible for more global misfolding of the protein, reflecting their sequence positions in the structure of the protein. Our results suggest that disease-related mutations in the α/β-hydrolase fold domain share common trafficking deficiencies yet lead to discrete congenital disorders of differing severity in the endocrine and nervous systems. Despite great functional diversity, characterization of the α/β-hydrolase fold proteins that encompass a superfamily of hydrolases, heterophilic adhesion proteins, and chaperone domains reveals a common structural motif. By incorporating the R451C mutation found in neuroligin (NLGN) and associated with autism and the thyroglobulin G2320R (G221R in NLGN) mutation responsible for congenital hypothyroidism into NLGN3, we show that mutations in the α/β-hydrolase fold domain influence folding and biosynthetic processing of neuroligin3 as determined by in vitro susceptibility to proteases, glycosylation processing, turnover, and processing rates. We also show altered interactions of the mutant proteins with chaperones in the endoplasmic reticulum and arrest of transport along the secretory pathway with diversion to the proteasome. Time-controlled expression of a fluorescently tagged neuroligin in hippocampal neurons shows that these mutations compromise neuronal trafficking of the protein, with the R451C mutation reducing and the G221R mutation virtually abolishing the export of NLGN3 from the soma to the dendritic spines. Although the R451C mutation causes a local folding defect, the G221R mutation appears responsible for more global misfolding of the protein, reflecting their sequence positions in the structure of the protein. Our results suggest that disease-related mutations in the α/β-hydrolase fold domain share common trafficking deficiencies yet lead to discrete congenital disorders of differing severity in the endocrine and nervous systems." @default.
• W2072856670 created "2016-06-24" @default.
• W2072856670 creator A5014315445 @default.
• W2072856670 creator A5035691434 @default.
• W2072856670 creator A5047777926 @default.
• W2072856670 creator A5049372570 @default.
• W2072856670 creator A5051156147 @default.
• W2072856670 creator A5056643482 @default.
• W2072856670 creator A5061736694 @default.
• W2072856670 creator A5073520854 @default.
• W2072856670 creator A5077645102 @default.
• W2072856670 creator A5082332482 @default.
• W2072856670 date "2010-09-01" @default.
• W2072856670 modified "2023-10-17" @default.
• W2072856670 title "Neuroligin Trafficking Deficiencies Arising from Mutations in the α/β-Hydrolase Fold Protein Family" @default.
• W2072856670 cites W1253615 @default.
• W2072856670 cites W1546139069 @default.
• W2072856670 cites W1966277592 @default.
• W2072856670 cites W1972878203 @default.
• W2072856670 cites W1978408031 @default.
• W2072856670 cites W1979158821 @default.
• W2072856670 cites W1980842944 @default.
• W2072856670 cites W1985807928 @default.
• W2072856670 cites W1987314226 @default.
• W2072856670 cites W1988011192 @default.
• W2072856670 cites W1991721037 @default.
• W2072856670 cites W1992551226 @default.
• W2072856670 cites W1993415479 @default.
• W2072856670 cites W1996092810 @default.
• W2072856670 cites W2005603079 @default.
• W2072856670 cites W2013336853 @default.
• W2072856670 cites W2029451118 @default.
• W2072856670 cites W2035243143 @default.
• W2072856670 cites W2036879415 @default.
• W2072856670 cites W2055474304 @default.
• W2072856670 cites W2055720472 @default.
• W2072856670 cites W2071767667 @default.
• W2072856670 cites W2072086952 @default.
• W2072856670 cites W2073190114 @default.
• W2072856670 cites W2083254788 @default.
• W2072856670 cites W2087510854 @default.
• W2072856670 cites W2090425242 @default.
• W2072856670 cites W2094366691 @default.
• W2072856670 cites W2096985729 @default.
• W2072856670 cites W2097789207 @default.
• W2072856670 cites W2100414555 @default.
• W2072856670 cites W2101407138 @default.
• W2072856670 cites W2104740195 @default.
• W2072856670 cites W2108013176 @default.
• W2072856670 cites W2108339073 @default.
• W2072856670 cites W2111683208 @default.
• W2072856670 cites W2116835533 @default.
• W2072856670 cites W2122818844 @default.
• W2072856670 cites W2125147395 @default.
• W2072856670 cites W2127038438 @default.
• W2072856670 cites W2129700237 @default.
• W2072856670 cites W2137207996 @default.
• W2072856670 cites W2156617634 @default.
• W2072856670 cites W2414307244 @default.
• W2072856670 cites W4230194875 @default.
• W2072856670 cites W4250374989 @default.
• W2072856670 cites W4253576098 @default.
• W2072856670 doi "https://doi.org/10.1074/jbc.m110.139519" @default.
• W2072856670 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/2937894" @default.
• W2072856670 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/20615874" @default.
• W2072856670 hasPublicationYear "2010" @default.
• W2072856670 type Work @default.
• W2072856670 sameAs 2072856670 @default.
• W2072856670 citedByCount "39" @default.
• W2072856670 countsByYear W20728566702012 @default.
• W2072856670 countsByYear W20728566702013 @default.
• W2072856670 countsByYear W20728566702014 @default.
• W2072856670 countsByYear W20728566702015 @default.
• W2072856670 countsByYear W20728566702016 @default.
• W2072856670 countsByYear W20728566702017 @default.
• W2072856670 countsByYear W20728566702018 @default.
• W2072856670 countsByYear W20728566702019 @default.
• W2072856670 countsByYear W20728566702020 @default.
• W2072856670 countsByYear W20728566702021 @default.
• W2072856670 countsByYear W20728566702022 @default.
• W2072856670 crossrefType "journal-article" @default.
• W2072856670 hasAuthorship W2072856670A5014315445 @default.
• W2072856670 hasAuthorship W2072856670A5035691434 @default.
• W2072856670 hasAuthorship W2072856670A5047777926 @default.
• W2072856670 hasAuthorship W2072856670A5049372570 @default.
• W2072856670 hasAuthorship W2072856670A5051156147 @default.
• W2072856670 hasAuthorship W2072856670A5056643482 @default.
• W2072856670 hasAuthorship W2072856670A5061736694 @default.
• W2072856670 hasAuthorship W2072856670A5073520854 @default.
• W2072856670 hasAuthorship W2072856670A5077645102 @default.
• W2072856670 hasAuthorship W2072856670A5082332482 @default.
• W2072856670 hasBestOaLocation W20728566701 @default.
• W2072856670 hasConcept C104317684 @default.
• W2072856670 hasConcept C112592302 @default.
• W2072856670 hasConcept C143065580 @default.
• W2072856670 hasConcept C158617107 @default.
• W2072856670 hasConcept C170493617 @default.
• W2072856670 hasConcept C171897839 @default.

• next