A5074877384- Cellular transport and secretion
- Lysosomal Storage Disorders Research
- Calcium signaling and nucleotide metabolism
- Glycosylation and Glycoproteins Research
- Amyotrophic Lateral Sclerosis Research
- Autophagy in Disease and Therapy
Harvard University
2022
Osnabrück University
2016-2020
Abstract Haploinsufficiency of GRN causes frontotemporal dementia (FTD). The locus produces progranulin (PGRN), which is cleaved to lysosomal granulin polypeptides. function granulins and why their absence neurodegeneration are unclear. Here we discover that PGRN-deficient human cells murine brains, as well frontal lobes from -mutation FTD patients have increased levels gangliosides, glycosphingolipids contain sialic acid. In these tissues, enzymes catabolize gangliosides were normal, but...
Organelles of the endomembrane system maintain their identity and integrity during growth or stress conditions by homeostatic mechanisms that regulate membrane flux biogenesis. At lysosomes endosomes, Fab1 lipid kinase complex nutrient-regulated target rapamycin 1 (TORC1) control endolysosomal homeostasis cellular metabolism. Both complexes are functionally connected as Fab1-dependent generation PI(3,5)P2 supports TORC1 activity. Here, we identify a on signaling which distinct from...