Basic fibroblast growth factor elicits formation of interstitial axonal branches via enhanced severing of microtubules.
The formation of interstitial axonal branches involves the severing of microtubules at sites where new branches form. Here we wished to ascertain whether basic fibroblast growth factor (bFGF) enhances axonal branching through alterations in proteins involved in the severing of microtubules. We found that treatment of cultured hippocampal neurons with bFGF heightens expression of both katanin and spastin, which are proteins that sever microtubules in the axon. In addition, treatment with bFGF enhances phosphorylation of tau at sites expected to cause it to dissociate from microtubules. This is important because tau regulates the access of katanin to the microtubule. In live-cell imaging experiments, axons of neurons treated with bFGF displayed greater numbers of dynamic free ends of microtubules, as well as greater numbers of short mobile microtubules. Entirely similar enhancement of axonal branching, short microtubule transport, and frequency of microtubule ends was observed when spastin was overexpressed in the neurons. Depletion of either katanin or spastin with siRNA diminished but did not eliminate the enhancement in branching elicited by bFGF. Collectively, these results indicate that bFGF enhances axonal branch formation by augmenting the severing of microtubules through both a spastin-based mode and a katanin-based mode.
Qiang
Liang
L
Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PA 19129, USA.
Yu
Wenqian
W
Liu
Mei
M
Solowska
Joanna M
JM
Baas
Peter W
PW
D000251:Adenosine Triphosphatases / Q000378:metabolism; D000818:Animals; D001369:Axons / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism*; D001692:Biological Transport / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D006624:Hippocampus / Q000166:cytology; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008870:Microtubules / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D016875:tau Proteins / Q000378:metabolism
C534832:Mapre3 protein, rat; D008869:Microtubule-Associated Proteins; D016875:tau Proteins; D016222:Fibroblast Growth Factor 2; D000251:Adenosine Triphosphatases