Molecular insights into the regulation of GNPTαβ by LYSET - PubMed
a day ago
- #lysosomal enzymes
- #mannose-6-phosphate pathway
- #Golgi membrane protein
- LYSET is a two-transmembrane protein essential for GNPT stability, cleavage by Site-1 Protease (S1P), and enzymatic activity.
- LYSET enhances GNPT cleavage and prevents its mislocalization to lysosomes for degradation.
- LYSET interacts with GOLPH3 and retromer complexes to anchor the LYSET-GNPT complex at the Golgi.
- An F4XXR7 motif in LYSET's N-tail is identified for GOLPH3 binding.
- The retromer promotes Golgi retention by binding to the C-terminal of LYSET and recycling it from endolysosomes.
- LYSET plays a multifaceted role in stabilizing GNPT, retaining it at the Golgi, and ensuring the fidelity of the M6P pathway.