CNS neuronal focal adhesion kinase forms clusters that co-localize with vinculin.
Focal adhesion kinase (FAK) is a non-receptor protein tyrosine kinase that appears to play a central role in integrin-mediated signal transduction in non-neuronal cells, linking the extracellular matrix to the actin-based cytoskeleton at focal adhesion contacts. Biochemical analysis has revealed the presence of FAK immunoreactivity in cells of neuronal lineage (Zhang et al., 1994) and in the CNS (Burgaya et al. 1995; Grant et al., 1995). In the current work, we have examined the immunodistribution of FAK in nerve cell cultures and tissue sections from the rat CNS. Cultures of B103 CNS neuroblastoma cells and primary cultures of hippocampal neurons both showed abundant FAK immunoreactivity in nerve cell bodies. Immunoreactivity also extended into neurites and growth cones. The most striking feature of FAK distribution was the presence of short, punctate clusters of high FAK concentration. These FAK clusters were maintained in triton-extracted cell ghosts, indicating association with the cytoskeleton. Double-label confocal imaging showed that clusters of FAK coincided with clusters of vinculin, another actin-associated signal transduction molecule implicated in control of growth cone motility. Data from hippocampal sections verified the presence of FAK in adult neurons where it was enriched in somato-dendritic domains and showed a non-uniform distribution. Quantitative FAK immunoprecipitation to compare adult with embryonic brain showed a 7-fold developmental down-regulation of FAK and a 21-fold down-regulation of FAK TyrP. The data suggest that neuronal FAK may participate in signal transduction complexes relevant to neuronal morphogenesis and plasticity.
Stevens
G R
GR
Department of Neurobiology and Physiology, Northwestern University, Evanston, Illinois 60208, USA.
Zhang
C
C
Berg
M M
MM
Lambert
M P
MP
Barber
K
K
Cantallops
I
I
Routtenberg
A
A
Klein
W L
WL
D000367:Age Factors; D000818:Animals; D001692:Biological Transport; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D003599:Cytoskeleton / Q000378:metabolism; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D018507:Gene Expression Regulation, Developmental; D006624:Hippocampus / Q000166:cytology / Q000196:embryology / Q000378:metabolism*; D046911:Macromolecular Substances; D018613:Microscopy, Confocal; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009447:Neuroblastoma / Q000378:metabolism / Q000473:pathology; D009473:Neuronal Plasticity; D009474:Neurons / Q000378:metabolism / Q000648:ultrastructure; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000502:physiology; D014407:Tumor Cells, Cultured; D016596:Vinculin / Q000378:metabolism*
D015815:Cell Adhesion Molecules; D046911:Macromolecular Substances; D009419:Nerve Tissue Proteins; D016596:Vinculin; D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496052:Ptk2 protein, rat