RT Journal Article
SR Electronic
T1 Fibroblast Growth Factor-Regulated Palmitoylation of the Neural Cell Adhesion Molecule Determines Neuronal Morphogenesis
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 8897
OP 8907
DO 10.1523/JNEUROSCI.2171-08.2008
VO 28
IS 36
A1 Evgeni Ponimaskin
A1 Galina Dityateva
A1 Mika O. Ruonala
A1 Masaki Fukata
A1 Yuko Fukata
A1 Fritz Kobe
A1 Fred S. Wouters
A1 Markus Delling
A1 David S. Bredt
A1 Melitta Schachner
A1 Alexander Dityatev
YR 2008
UL http://www.jneurosci.org/content/28/36/8897.abstract
AB During development of the nervous system, short- and long-range signals cooperate to promote axonal growth, guidance, and target innervation. Particularly, a short-range signal transducer, the neural cell adhesion molecule (NCAM), stimulates neurite outgrowth via mechanisms that require posttranslational modification of NCAM and signaling via receptors to a long-range messenger, the fibroblast growth factor (FGF). In the present study we further characterized a mechanism which regulates the functional interplay between NCAM and FGF receptor(s). We show that activation of FGF receptor(s) by FGF2 leads to palmitoylation of the two major transmembrane NCAM isoforms, NCAM140 and NCAM180, translocation of NCAM to GM1 ganglioside-containing lipid rafts, and stimulation of neurite outgrowth of hippocampal neurons. Ablation of NCAM, mutation of NCAM140 or NCAM180 palmitoylation sites, or pharmacological suppression of NCAM signaling inhibited FGF2-stimulated neurite outgrowth. Of the 23 members of the aspartate-histidine-histidine-cysteine (DHHC) domain containing proteins, DHHC-7 most strongly stimulated palmitoylation of NCAM, and enzyme activity was enhanced by FGF2. Thus, our study uncovers a molecular mechanism by which a growth factor regulates neuronal morphogenesis via activation of palmitoylation, which in turn modifies subcellular location and thus signaling via an adhesion molecule.