Sandra Pohl

TL;DR: It is found that the α/β-subunit precursor is cleaved by the site-1 protease (S1P) that activates sterol regulatory element–binding proteins in response to cholesterol deprivation, which functions in the biogenesis of lysosomes, and lipid-independent phenotypes of S1P deficiency may be caused by lysOSomal dysfunction.

TL;DR: The generation of recombinant single-chain antibody fragments against M6P residues and of new mouse models of MLII and MLIII will have considerable impact to provide deeper insight into the cell biology of lysosomal dysfunctions and the pathomechanisms underlying these lysOSomal disorders.

TL;DR: The finding that an increased neuronal level of the microtubule-associated protein 1 light chain 3 and the formation of p62-positive neuronal aggregates indicate an impairment of constitutive autophagy in the mucolipidosis II brain demonstrates the essential role of mannose 6-phosphate for selected lysosomal proteins to maintain the capability for degradation of sequestered components in lysOSomes and autophagolysosomes and prevent neurodegeneration.

TL;DR: It is reported that a novel type of dileucine-based sorting motif, EEEX8LI, present in the second cytoplasmic domain of CLN3, is sufficient for proper targeting to lysosomes and revealed that lysOSomal sorting motifs located in an intramolecular cy toplasmics domain of a multimembrane-spanning protein have different structural requirements for adaptor binding than sorting signals found in the C-terminal cytop

TL;DR: Findings indicate that differential perturbations of distinct signaling pathways might alter disease progression and provide insight into the molecular alterations underlying neuronal dysfunction in CLN3 disease and neurodegeneration in general.