PMID- 12359136
OWN - NLM
STAT- MEDLINE
DCOM- 20030527
LR  - 20191106
IS  - 1096-7192 (Print)
IS  - 1096-7192 (Linking)
VI  - 77
IP  - 1-2
DP  - 2002 Sep-Oct
TI  - Unraveling the molecular pathogenesis of free sialic acid storage disorders: 
      altered targeting of mutant sialin.
PG  - 99-107
AB  - Salla disease (SD) and infantile sialic acid storage disease (ISSD) are 
      recessively inherited, neuro-degenerative disorders caused by mutations in the 
      SLC17A5 gene. The gene product, sialin, is a lysosomal membrane protein which 
      transports free sialic acid across the membrane. Although the function of sialin 
      is basically known, the details of biosynthesis and intracellular trafficking as 
      well as functional consequences of disease mutations in the SLC17A5 gene are not 
      characterized. Here we studied for the first time the expression, localization, 
      and targeting of the wild-type sialin as well as two mutant polypeptides; one 
      mimicking the Finnish founder mutation, R39C (Salla(FIN)), and the other a 
      deletion (del268-272) found in ISSD patients using in vitro expression of the 
      corresponding cDNA constructs. The wild-type sialin was targeted to lysosomes 
      whereas a significant fraction of the Salla(FIN) polypeptides and the majority of 
      the ISSD polypeptides remained in the Golgi compartment. Further, using a 
      temperature block of intracellular transport, we observed that the rate of the 
      trafficking of the mutant polypeptides to lysosomes is significantly slower than 
      that of their wild-type counterpart. These findings are in line with the 
      phenotypic differences between SD and ISSD, the former presenting mental 
      retardation with long life span in contrast to the latter being an early fatal 
      disorder.
FAU - Aula, Nina
AU  - Aula N
AD  - Department of Molecular Medicine, Biomedicum, National Public Health Institute, 
      Haartmaninkatu 8, 00290, Helsinki, Finland. Nina.Aula@ktl.fi
FAU - Jalanko, Anu
AU  - Jalanko A
FAU - Aula, Pertti
AU  - Aula P
FAU - Peltonen, Leena
AU  - Peltonen L
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Mol Genet Metab
JT  - Molecular genetics and metabolism
JID - 9805456
RN  - 0 (DNA, Complementary)
RN  - 0 (Organic Anion Transporters)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Symporters)
RN  - 0 (sialic acid transport proteins)
RN  - GZP2782OP0 (N-Acetylneuraminic Acid)
SB  - IM
CIN - Mol Genet Metab. 2004 Jun;82(2):99-100. PMID: 15171996
MH  - Animals
MH  - Base Sequence
MH  - COS Cells
MH  - Cell Line
MH  - Cricetinae
MH  - DNA, Complementary/genetics
MH  - Golgi Apparatus/metabolism
MH  - HeLa Cells
MH  - Humans
MH  - In Vitro Techniques
MH  - Lysosomes/metabolism
MH  - Models, Molecular
MH  - Molecular Weight
MH  - *Mutation
MH  - N-Acetylneuraminic Acid/metabolism
MH  - Organic Anion Transporters/chemistry/*genetics/*metabolism
MH  - Recombinant Proteins/chemistry/genetics/metabolism
MH  - Sialic Acid Storage Disease/etiology/*genetics/*metabolism
MH  - Symporters/chemistry/*genetics/*metabolism
MH  - Transfection
EDAT- 2002/10/03 04:00
MHDA- 2003/05/28 05:00
CRDT- 2002/10/03 04:00
PHST- 2002/10/03 04:00 [pubmed]
PHST- 2003/05/28 05:00 [medline]
PHST- 2002/10/03 04:00 [entrez]
AID - S1096719202001245 [pii]
AID - 10.1016/s1096-7192(02)00124-5 [doi]
PST - ppublish
SO  - Mol Genet Metab. 2002 Sep-Oct;77(1-2):99-107. doi: 10.1016/s1096-7192(02)00124-5.