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- Title
The lysosomal trafficking of sphingolipid activator proteins (SAPs) is mediated by sortilin.
- Authors
Stephane Lefrancois; Jibin Zeng; A.Jacob Hassan; Maryssa Canuel; Carlos R. Morales
- Abstract
Most soluble lysosomal proteins bind the mannose 6-phosphate receptor (M6P-R) to be sorted to the lysosomes. However, the lysosomes of I-cell disease (ICD) patients, a condition resulting from a mutation in the phosphotransferase that adds mannose 6-phosphate to hydrolases, have near normal levels of several lysosomal proteins, including the sphingolipid activator proteins (SAPs), G<inf>M2</inf>AP and prosaposin. We tested the hypothesis that SAPs are targeted to the lysosomal compartment via the sortilin receptor. To test this hypothesis, a dominant-negative construct of sortilin and a sortilin small interfering RNA (siRNA) were introduced into COS-7 cells. Our results showed that both the truncated sortilin and the sortilin siRNA block the traffic of G<inf>M2</inf>AP and prosaposin to the lysosomal compartment. This observation was confirmed by a co-immunoprecipitation, which demonstrated that G<inf>M2</inf>AP and prosaposin are interactive partners of sortilin. Furthermore, a dominant-negative mutant GGA prevented the trafficking of prosaposin and G<inf>M2</inf>AP to lysosomes. In conclusion, our results show that the trafficking of SAPs is dependent on sortilin, demonstrating a novel lysosomal trafficking.
- Publication
EMBO Journal, 2003, Vol 22, Issue 24, p6430
- ISSN
0261-4189
- Publication type
Academic Journal
- DOI
10.1093/emboj/cdg629