A synthetic peptide corresponding to residues 301-320 of human Wnt-1 promotes PC12 cell adhesion and hippocampal neural stem cell differentiation.
Wnt signaling cascades play a crucial role in the maintenance of stem cell niches in many tissues as well as in embryonic patterning and cell-fate determination. Wnt signaling pathways have been well studied; however, the precise binding mechanism of Wnt protein to its receptor has not yet been clarified. Here we show the design and synthesis of seven novel peptide candidates for a receptor-binding site of human Wnt-1 based on its hydrophilicity and beta-turn profiles. Among these Wnt-derived peptides, only WP7, which corresponds to residues 301-320 of human Wnt-1, bound to the soluble receptor for Wnt-1, mouse Frizzled-1/Fc chimera, promoted PC12 cell adherence, increased level of cytosolic beta-catenin in PC12 cells, and induced adhesion and neuronal differentiation of hippocampal neural precursor cells. These results suggest that residues 301-320 of human Wnt-1 is one of the receptor-binding sites and that WP7 may activate the canonical Wnt pathway. When combined with an appropriate matrix, the action of this Wnt-derived peptide, WP7, can be limited to within a location, and therefore could be useful in the regeneration of many tissues, without fear of tumor generation.
Kajiwara
Kazumi
K
Graduate School of Materials Science, Nara Institute of Science and Technology, 8916-5 Takayama, Ikoma, Nara 630-0192, Japan.
Kamamoto
Maiko
M
Ogata
Shin-ichi
S
Tanihara
Masao
M
D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects*; D002454:Cell Differentiation / Q000187:drug effects*; D006624:Hippocampus / Q000166:cytology; D006801:Humans; D016716:PC12 Cells; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D051155:Wnt1 Protein / Q000502:physiology*; D051176:beta Catenin / Q000378:metabolism
D010446:Peptide Fragments; D051155:Wnt1 Protein; D051176:beta Catenin