PMID: 20406422

 

    Legend: Gene, Sites

Title : Lysosomal targeting of the CLN7 membrane glycoprotein and transport via the plasma membrane require a dileucine motif

Abstract :
  1. CLN7 is a polytopic lysosomal membrane protein deficient in variant late infantile neuronal ceroid lipofuscinosis, a neurodegenerative lysosomal storage disorder
  2. In this study fluorescence protease protection assays and mutational analyses revealed the N- and C-terminal tails of CLN7 in the cytosol and two N-glycosylation sites at N371 and N376
  3. Both partially and non-glycosylated CLN7 were correctly transported to lysosomes
  4. To identify lysosomal targeting motifs , we generated CD4-chimera fused to the N- and C-terminal domains of CLN7
  5. Lysosomal localization of the chimeric proteins requires a consensus acidic dileucine-based motif in the N-terminus and two tandem tyrosine-based signals in the C-terminus
  6. Mutation of these sorting motifs resulted in cell surface redistribution of CD4 chimeras
  7. However, the dileucine-based motif is of critical importance for lysosomal localization of the full-length CLN7 in different cell lines
  8. Cell surface biotinylation revealed that at equilibrium 22% of total CLN7 is localized at the plasma membrane
  9. Mutation of the dileucine motif or the co-expression of dominant-negative mutant dynamin K44A led to a further increase of CLN7 at the plasma membrane
  10. Our data demonstrate that CLN7 contains several cytoplasmic lysosomal targeting signals of which the N-terminal dileucine-based motif is required for the predominant lysosomal targeting along the indirect pathway and clathrin-mediated endocytosis of CLN7
Output (sent_index, trigger, protein, sugar, site):
  • 0. glycoprotein, , glycoprotein, -, -
  • 2. N-glycosylation, , -, -, N371 and N376
  • 2. N-glycosylation, , CLN7, -, N371 and N376
  • 2. N-glycosylation, , CLN7, -, sites
  • 3. non-glycosylated, , CLN7, -, -
Output(Part-Of) (sent_index, protein, site):
  • 2. CLN7, N371 and N376
  • 2. CLN7, sites
  • 2. CLN7, tails
  • 4. CLN7, domains
*Output_Site_Fusion* (sent_index, protein, sugar, site):
  • 2. CLN7, -, N371 and N376

 

 

Protein NCBI ID SENTENCE INDEX
CLN7 256471 0,1,2,3,4,7,8,9,10
CD4 920 4,6