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CLN3p impacts galactosylceramide transport, raft morphology, and lipid content.

Publication ,  Journal Article
Rusyn, E; Mousallem, T; Persaud-Sawin, D-A; Miller, S; Boustany, R-MN
Published in: Pediatr Res
June 2008

Juvenile neuronal ceroid lipofuscinosis (JNCL) belongs to the neuronal ceroid lipofuscinoses characterized by blindness/seizures/motor/cognitive decline and early death. JNCL is caused by CLN3 gene mutations that negatively modulate cell growth/apoptosis. CLN3 protein (CLN3p) localizes to Golgi/Rab4-/Rab11-positive endosomes and lipid rafts, and harbors a galactosylceramide (GalCer) lipid raft-binding domain. Goals are proving CLN3p participates in GalCer transport from Golgi to rafts, and GalCer deficits negatively affect cell growth/apoptosis. GalCer/mutant CLN3p are retained in Golgi, with CLN3p rescuing GalCer deficits in rafts. Diminishing GalCer in normal cells by GalCer synthase siRNA negatively affects cell growth/apoptosis. GalCer restores JNCL cell growth. WT CLN3p binds GalCer, but not mutant CLN3p. Sphingolipid content of rafts/Golgi is perturbed with diminished GalCer in rafts and accumulation in Golgi. CLN3-deficient raft vesicular structures are small by transmission electron microscopy, reflecting altered sphingolipid composition of rafts. CLN1/CLN2/CLN6 proteins bind to lysophosphatidic acid/sulfatide, CLN6/CLN8 proteins to GalCer, and CLN8 protein to ceramide. Sphingolipid composition/morphology of CLN1-/CLN2-/CLN6-/CLN8- and CLN9-deficient rafts are altered suggesting changes in raft structure/lipid stoichiometry could be common themes underlying these diseases.

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Published In

Pediatr Res

DOI

ISSN

0031-3998

Publication Date

June 2008

Volume

63

Issue

6

Start / End Page

625 / 631

Location

United States

Related Subject Headings

  • Tripeptidyl-Peptidase 1
  • Sulfoglycosphingolipids
  • Subcellular Fractions
  • Protein Transport
  • Protein Binding
  • Pediatrics
  • Neuronal Ceroid-Lipofuscinoses
  • Mutation
  • Molecular Chaperones
  • Mice, Knockout
 

Citation

APA
Chicago
ICMJE
MLA
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Rusyn, E., Mousallem, T., Persaud-Sawin, D.-A., Miller, S., & Boustany, R.-M. (2008). CLN3p impacts galactosylceramide transport, raft morphology, and lipid content. Pediatr Res, 63(6), 625–631. https://doi.org/10.1203/PDR.0b013e31816fdc17
Rusyn, Elena, Talal Mousallem, Dixie-Ann Persaud-Sawin, Sara Miller, and Rose-Mary N. Boustany. “CLN3p impacts galactosylceramide transport, raft morphology, and lipid content.Pediatr Res 63, no. 6 (June 2008): 625–31. https://doi.org/10.1203/PDR.0b013e31816fdc17.
Rusyn E, Mousallem T, Persaud-Sawin D-A, Miller S, Boustany R-MN. CLN3p impacts galactosylceramide transport, raft morphology, and lipid content. Pediatr Res. 2008 Jun;63(6):625–31.
Rusyn, Elena, et al. “CLN3p impacts galactosylceramide transport, raft morphology, and lipid content.Pediatr Res, vol. 63, no. 6, June 2008, pp. 625–31. Pubmed, doi:10.1203/PDR.0b013e31816fdc17.
Rusyn E, Mousallem T, Persaud-Sawin D-A, Miller S, Boustany R-MN. CLN3p impacts galactosylceramide transport, raft morphology, and lipid content. Pediatr Res. 2008 Jun;63(6):625–631.

Published In

Pediatr Res

DOI

ISSN

0031-3998

Publication Date

June 2008

Volume

63

Issue

6

Start / End Page

625 / 631

Location

United States

Related Subject Headings

  • Tripeptidyl-Peptidase 1
  • Sulfoglycosphingolipids
  • Subcellular Fractions
  • Protein Transport
  • Protein Binding
  • Pediatrics
  • Neuronal Ceroid-Lipofuscinoses
  • Mutation
  • Molecular Chaperones
  • Mice, Knockout