PMID- 15510212
OWN - NLM
STAT- MEDLINE
DCOM- 20050628
LR  - 20181113
IS  - 0261-4189 (Print)
IS  - 1460-2075 (Electronic)
IS  - 0261-4189 (Linking)
VI  - 23
IP  - 23
DP  - 2004 Nov 24
TI  - Functional characterization of wild-type and mutant human sialin.
PG  - 4560-70
AB  - The modification of cell surface lipids or proteins with sialic acid is essential 
      for many biological processes and several diseases are caused by defective sialic 
      acid metabolism. Sialic acids cleaved off from degraded sialoglycoconjugates are 
      exported from lysosomes by a membrane transporter, named sialin, which is 
      defective in two allelic inherited diseases: infantile sialic acid storage 
      disease (ISSD) and Salla disease. To develop a functional assay of human sialin, 
      we redirected the protein to the plasma membrane by mutating a dileucine-based 
      internalization motif. Cells expressing the plasmalemmal construct accumulated 
      neuraminic acid at acidic pH by a process equivalent to lysosomal efflux. The 
      assay was used to determine how pathogenic mutations affect transport. 
      Interestingly, while two missense mutations and one small, in-frame deletion 
      associated with ISSD abolished transport, the mutation causing Salla disease 
      (R39C) slowed down, but did not stop, the transport cycle, thus explaining why 
      the latter disorder is less severe. Since neurological symptoms predominate in 
      Salla disease, our results suggest that sialin is rate-limiting to specific 
      sialic acid-dependent processes of the nervous system.
FAU - Morin, Pierre
AU  - Morin P
AD  - CNRS UPR 1929, Institut de Biologie Physico-Chimique, Paris, France.
FAU - Sagne, Corinne
AU  - Sagne C
FAU - Gasnier, Bruno
AU  - Gasnier B
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20041028
PL  - England
TA  - EMBO J
JT  - The EMBO journal
JID - 8208664
RN  - 0 (Organic Anion Transporters)
RN  - 0 (Sialic Acids)
RN  - 0 (Symporters)
RN  - 0 (sialic acid transport proteins)
SB  - IM
MH  - Amino Acid Motifs
MH  - Cell Line
MH  - Cell Membrane/metabolism
MH  - Cloning, Molecular
MH  - Endocytosis
MH  - Humans
MH  - Hydrogen-Ion Concentration
MH  - Mutation
MH  - Organic Anion Transporters/genetics/*metabolism
MH  - Protein Transport
MH  - Sialic Acid Storage Disease/genetics
MH  - Sialic Acids/metabolism
MH  - Symporters/genetics/*metabolism
PMC - PMC533050
EDAT- 2004/10/29 09:00
MHDA- 2005/06/29 09:00
PMCR- 2005/11/24
CRDT- 2004/10/29 09:00
PHST- 2004/06/18 00:00 [received]
PHST- 2004/10/07 00:00 [accepted]
PHST- 2004/10/29 09:00 [pubmed]
PHST- 2005/06/29 09:00 [medline]
PHST- 2004/10/29 09:00 [entrez]
PHST- 2005/11/24 00:00 [pmc-release]
AID - 7600464 [pii]
AID - 10.1038/sj.emboj.7600464 [doi]
PST - ppublish
SO  - EMBO J. 2004 Nov 24;23(23):4560-70. doi: 10.1038/sj.emboj.7600464. Epub 2004 Oct 
      28.