Neurite guidance by the FnC repeat of human tenascin-C: neurite attraction vs. neurite retention.
The alternatively spliced fibronectin type-III repeat C of human tenascin-C (fnC) provides directional cues to elongating neurites in vitro. When given a choice at an interface with poly L-lysine (PLL), rat cerebellar granule neurites preferentially crossed onto fnC (defined herein as neurite attraction) whereas neurites originating on fnC preferentially remained on fnC (defined as neurite retention). Guidance motifs were further refined using synthetic peptides spanning the sequence of fnC. We found that a peptide with amino acid sequence DINPYGFTVSWMASE was sufficient to attract and retain neurites. Peptides with alterations in NPYG facilitated neurite retention but not attraction and, conversely, molecules with alterations in ASE facilitated neurite attraction but not retention. Hence neurite attraction and neurite retention mediated by fnC are separable events that can be independently regulated. This property may prove valuable for the strategic design of peptide reagents for use in strategies to facilitate directed axonal regrowth following CNS injury.
Liu
Hsing-Yin
HY
Department of Pharmacology, UMDNJ-Robert Wood Johnson Medical School, 675 Hoes Lane, Piscataway, NJ 08854, USA.
Nur-E-Kamal
Alam
A
Schachner
Melitta
M
Meiners
Sally
S
D017398:Alternative Splicing; D000595:Amino Acid Sequence / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology; D005353:Fibronectins / Q000502:physiology*; D006801:Humans; D008958:Models, Molecular; D016296:Mutagenesis / Q000502:physiology; D016501:Neurites / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000166:cytology* / Q000187:drug effects; D051381:Rats; D011994:Recombinant Proteins / Q000494:pharmacology; D013329:Structure-Activity Relationship; D019063:Tenascin / Q000737:chemistry* / Q000502:physiology*
D005353:Fibronectins; D011994:Recombinant Proteins; D019063:Tenascin; C501364:fibronectin type III like peptide, human