Conformational and amino acid residue requirements for the saposin C neuritogenic effect.

  title={Conformational and amino acid residue requirements for the saposin C neuritogenic effect.},
  author={X. Qi and K. Kondoh and D. Krusling and G. Kelso and T. Leonova and G. Grabowski},
  volume={38 19},
Prosaposin is the precursor of four activator proteins, termed saposins A, B, C, and D, that are required for much of glycosphingolipid hydrolysis. The intact precursor also has neurite outgrowth activity ex vivo and in vivo that is localized to amino acid residues 22-31 of saposin C. Across species, this saposin C region has a high degree of identity and similarity with amino acids in the analogous region of saposin A. Wild-type and mutant saposins C and A from human and mouse were expressed… Expand
Ex vivo localization of the mouse saposin C activation region for acid beta-glucosidase.
Results show that the transgenic prosaposins were expressed and processed to functional saposins in fibroblasts and that the enzymatic activation domain is located at carboxyl-terminal half of saposin C and functions only in the context of the general saposIn structure. Expand
Differential Membrane Interactions of Saposins A and C
Findings show that proper orientation of the middle segment of saposin C to the outside of the membrane surface is critical for its specific and multivalent interaction with acid β-glucosidase. Expand
Role of lysine residues in membrane anchoring of saposin C.
Results indicate that positively charged amino acids at positions 13 and 17 are required for the fusogenic function of saposin C, and the side-chain structure of lysine is crucial to the precise membrane anchoring which is necessary for the total fusion activity of saPOSin C. Expand
Fusogenic domain and lysines in saposin C.
Saposin C's fusogenic and activation functions have different requirements for the orientation and insertion manners of helical peptides in membranes, suggesting the segregation of the fusion and activation function into two different regions of saposin C. Expand
Prosaposin: threshold rescue and analysis of the "neuritogenic" region in transgenic mice.
The degree of neuropathologic manifestations in each transgenic line depended on expression level rather than on the nature of the transgene, and in vivo localization of the GCase activation region to the carboxy terminal half of saposin C and the lack of a significant gross trophic effect of saPOSin C on CNS organization in vivo are shown. Expand
Conservation of expression and alternative splicing in the prosaposin gene.
There is evolutionary conservation of the prosaposin structure and alternative splicing in chick and zebrafish as well as in mouse and chick developing brain, and the results indicate that, in mouse brain, skeletal and cardiac muscle the exon 8-containing RNA is most abundant, while it is almost absent from visceral and smooth muscle-containing organs. Expand
Molecular and cell biology of acid beta-glucosidase and prosaposin.
  • X. Qi, G. Grabowski
  • Biology, Medicine
  • Progress in nucleic acid research and molecular biology
  • 2001
The chapter discusses the molecular biologic, biochemical, and cell biology approaches to evaluate the disordered metabolism of the proteins and lipids that have resulted in Gaucher disease. Expand
Phospholipid membrane interactions of saposin C: in situ atomic force microscopic study.
The results indicated that H2 contributed to domain formation but not to membrane destabilization, whereas H1 induced neither type of membrane restructuring, whereas patch-like domain formation was independent of acidic phospholipids, whereas membranes destabilization is dependent on the presence and concentration of acidic phosphorus. Expand
Saposin C: Neuronal Effect and CNS Delivery by Liposomes
Delivery of saposin C ex vivo into cultured neurons and in vivo into brain neuronal cells in mice across the blood‐brain barrier was accomplished with intravenously administered dioleoylphosphatidylserine (DOPS) liposomes to yield a new therapeutic approach for neuron protection, preservation, and regeneration. Expand
Molecular imaging of membrane interfaces reveals mode of β-glucosidase activation by saposin C
In situ atomic force microscopy and FRET data support a mechanism in which sapC locally alters regions of bilayer for subsequent attack by the enzyme in stably bound protein complexes. Expand