The secretion and maturation of prosaposin and procathepsin D are blocked in embryonic neural progenitor cells.
The notion that prosaposin (Prosap) is likely involved in brain development and regeneration led us to explore its expression in stem/progenitor neural cells and its fate after cell differentiation. The expression of procathepsin-cathepsin D (proCath-Cath D), an endoprotease that plays an important role in the processing and sorting of Prosap, has been concomitantly examined. Our data evidenced that in embryonic human neural progenitor cells (eHNPCs) intact and high molecular weight intermediate forms of Prosap and intermediate forms of Cath D accumulated inside the cells, while the formation of saposins and mature Cath D was impaired. Furthermore, neither Prosap nor proCath D were secreted from eHNPCs. The block of the processing and secretion shared by Prosap and proCath D was overcome during the course of differentiation of eHNPCs into a mixed population of astrocytes and neuronal cells. Upon differentiation, large amounts of Prosap and proCath D were secreted from the cells, while saposins and mature Cath D were produced inside the cells. The dramatic accumulation of Prosap (an antiapoptotic factor) and reduction of mature Cath D (a proapoptotic factor) in the undifferentiated eHNPCs most likely play a role in the molecular mechanisms regulating the resistance to apoptotic signals of these cells and might represent a critically important issue in HNPCs biology.
Salvioli
Rosa
R
Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore Sanità, Viale Regina Elena 299, 00161 Roma, Italy.
Ricci-Vitiani
Lucia
L
Tatti
Massimo
M
Scarpa
Susanna
S
De Maria
Ruggero
R
Vaccaro
Anna Maria
AM
D017398:Alternative Splicing; D002402:Cathepsin D / Q000032:analysis / Q000378:metabolism*; D002454:Cell Differentiation; D002478:Cells, Cultured; D004792:Enzyme Precursors / Q000032:analysis / Q000378:metabolism*; D006026:Glycoside Hydrolases / Q000378:metabolism; D006801:Humans; D009474:Neurons / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D009830:Olfactory Bulb / Q000166:cytology / Q000196:embryology; D011498:Protein Precursors / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D049231:Saposins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D013234:Stem Cells / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*
D004792:Enzyme Precursors; C483345:PSAP protein, human; D011498:Protein Precursors; D049231:Saposins; D006026:Glycoside Hydrolases; C058345:procathepsin D; D002402:Cathepsin D