FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W4322009528> ?p ?o ?g. }

• W4322009528 abstract "Progranulin (PGRN) is a lysosomal protein implicated in various neurodegenerative diseases. Over 70 mutations discovered in the GRN gene all result in reduced expression of PGRN protein. However, the detailed molecular function of PGRN within lysosomes and the impact of PGRN deficiency on lysosomal biology remain unclear. Here we leveraged multifaceted proteomic techniques to comprehensively characterize how PGRN deficiency changes the molecular and functional landscape of neuronal lysosomes. Using lysosome proximity labeling and immuno-purification of intact lysosomes, we characterized lysosome compositions and interactomes in both human induced pluripotent stem cell (iPSC)-derived glutamatergic neurons (i 3 Neurons) and mouse brains. Using dynamic stable isotope labeling by amino acids in cell culture (dSILAC) proteomics, we measured global protein half-lives in i 3 Neurons for the first time and characterized the impact of progranulin deficiency on neuronal proteostasis. Together, this study indicated that PGRN loss impairs the lysosome’s degradative capacity with increased levels of v-ATPase subunits on the lysosome membrane, increased catabolic enzymes within the lysosome, elevated lysosomal pH, and pronounced alterations in neuron protein turnover. Collectively, these results suggested PGRN as a critical regulator of lysosomal pH and degradative capacity, which in turn influences global proteostasis in neurons. The multi-modal techniques developed here also provided useful data resources and tools to study the highly dynamic lysosome biology in neurons." @default.
• W4322009528 created "2023-02-26" @default.
• W4322009528 creator A5009798873 @default.
• W4322009528 creator A5010767662 @default.
• W4322009528 creator A5027559254 @default.
• W4322009528 creator A5027663167 @default.
• W4322009528 creator A5028595660 @default.
• W4322009528 creator A5028723665 @default.
• W4322009528 creator A5030660240 @default.
• W4322009528 creator A5036265687 @default.
• W4322009528 creator A5045960665 @default.
• W4322009528 creator A5054664926 @default.
• W4322009528 creator A5074341729 @default.
• W4322009528 date "2023-02-24" @default.
• W4322009528 modified "2023-09-27" @default.
• W4322009528 title "Multi-modal Proteomic Characterization of Lysosomal Function and Proteostasis in Progranulin-Deficient Neurons" @default.
• W4322009528 cites W1523693806 @default.
• W4322009528 cites W1803199265 @default.
• W4322009528 cites W1900339045 @default.
• W4322009528 cites W1980496079 @default.
• W4322009528 cites W1987618579 @default.
• W4322009528 cites W1988007578 @default.
• W4322009528 cites W1988650085 @default.
• W4322009528 cites W1994823455 @default.
• W4322009528 cites W2005731595 @default.
• W4322009528 cites W2027460468 @default.
• W4322009528 cites W2040027262 @default.
• W4322009528 cites W2096578658 @default.
• W4322009528 cites W2099540110 @default.
• W4322009528 cites W2138948114 @default.
• W4322009528 cites W2326369813 @default.
• W4322009528 cites W2341088037 @default.
• W4322009528 cites W2554496886 @default.
• W4322009528 cites W2568579298 @default.
• W4322009528 cites W2588791993 @default.
• W4322009528 cites W2608066436 @default.
• W4322009528 cites W2737853846 @default.
• W4322009528 cites W2745248930 @default.
• W4322009528 cites W2749058695 @default.
• W4322009528 cites W2758918800 @default.
• W4322009528 cites W2760524820 @default.
• W4322009528 cites W2763924102 @default.
• W4322009528 cites W2766243612 @default.
• W4322009528 cites W2788593837 @default.
• W4322009528 cites W2801103925 @default.
• W4322009528 cites W2802961407 @default.
• W4322009528 cites W2803819386 @default.
• W4322009528 cites W2806543441 @default.
• W4322009528 cites W2808848024 @default.
• W4322009528 cites W2810440784 @default.
• W4322009528 cites W2891017487 @default.
• W4322009528 cites W2900569176 @default.
• W4322009528 cites W2906401896 @default.
• W4322009528 cites W2907108807 @default.
• W4322009528 cites W2952786943 @default.
• W4322009528 cites W2973356406 @default.
• W4322009528 cites W2982893839 @default.
• W4322009528 cites W2991456852 @default.
• W4322009528 cites W2997022986 @default.
• W4322009528 cites W3000377151 @default.
• W4322009528 cites W3003937758 @default.
• W4322009528 cites W3014984638 @default.
• W4322009528 cites W3035925528 @default.
• W4322009528 cites W3091987029 @default.
• W4322009528 cites W3100577602 @default.
• W4322009528 cites W3109441892 @default.
• W4322009528 cites W3115683357 @default.
• W4322009528 cites W3122919571 @default.
• W4322009528 cites W3142344578 @default.
• W4322009528 cites W3162043820 @default.
• W4322009528 cites W3164943245 @default.
• W4322009528 cites W3165179041 @default.
• W4322009528 cites W3179049001 @default.
• W4322009528 cites W3195683533 @default.
• W4322009528 cites W3197615719 @default.
• W4322009528 cites W4210958114 @default.
• W4322009528 cites W4211108138 @default.
• W4322009528 cites W4213136568 @default.
• W4322009528 cites W4220722570 @default.
• W4322009528 cites W4220846387 @default.
• W4322009528 cites W4283383357 @default.
• W4322009528 cites W4283702206 @default.
• W4322009528 cites W4283815489 @default.
• W4322009528 cites W4284882692 @default.
• W4322009528 cites W4284895216 @default.
• W4322009528 cites W4303446525 @default.
• W4322009528 doi "https://doi.org/10.1101/2023.02.24.529955" @default.
• W4322009528 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/36865171" @default.
• W4322009528 hasPublicationYear "2023" @default.
• W4322009528 type Work @default.
• W4322009528 citedByCount "1" @default.
• W4322009528 countsByYear W43220095282023 @default.
• W4322009528 crossrefType "posted-content" @default.
• W4322009528 hasAuthorship W4322009528A5009798873 @default.
• W4322009528 hasAuthorship W4322009528A5010767662 @default.
• W4322009528 hasAuthorship W4322009528A5027559254 @default.
• W4322009528 hasAuthorship W4322009528A5027663167 @default.
• W4322009528 hasAuthorship W4322009528A5028595660 @default.
• W4322009528 hasAuthorship W4322009528A5028723665 @default.
• W4322009528 hasAuthorship W4322009528A5030660240 @default.

• next