Elevated phenylalanine levels interfere with neurite outgrowth stimulated by the neuronal cell adhesion molecule L1 in vitro.
Elevated levels of phenylalanine (Phe) as observed in patients with phenylketonuria interfere with proper neuronal development, leading to severe psychomotor deficits and mental retardation. We have analyzed the effects of Phe on neurite outgrowth in vitro. When expressed in fibroblasts, the neuronal cell adhesion molecules L1 and plexin B3 strongly increase the length of neurites emanating from cerebellar neurons in co-culture experiments. Elevated Phe blocks L1-mediated, but not plexin B3-mediated outgrowth, whereas tyrosine is ineffective. Elevated Phe also interferes with aggregation of fibroblasts overexpressing L1, suggesting that the pathological effect of elevated Phe occurs by interfering with L1-mediated cell adhesion.
Hartwig
Christine
C
Institut für Humangenetik, Universitätsklinikum Hamburg-Eppendorf, Germany.
Gal
Andreas
A
Santer
Rene
R
Ullrich
Kurt
K
Finckh
Ulrich
U
Kreienkamp
Hans-Jürgen
HJ
D016475:3T3 Cells; D000818:Animals; D002448:Cell Adhesion; D051379:Mice; D008810:Mice, Inbred C57BL; D019006:Neural Cell Adhesion Molecules / Q000378:metabolism*; D016501:Neurites; D010649:Phenylalanine / Q000097:blood*
D019006:Neural Cell Adhesion Molecules; D010649:Phenylalanine