The microtubule-severing proteins spastin and katanin participate differently in the formation of axonal branches.
Neurons express two different microtubule-severing proteins, namely P60-katanin and spastin. Here, we performed studies on cultured neurons to ascertain whether these two proteins participate differently in axonal branch formation. P60-katanin is more highly expressed in the neuron, but spastin is more concentrated at sites of branch formation. Overexpression of spastin dramatically enhances the formation of branches, whereas overexpression of P60-katanin does not. The excess spastin results in large numbers of short microtubules, whereas the excess P60-katanin results in short microtubules intermingled with longer microtubules. We hypothesized that these different microtubule-severing patterns may be due to the presence of molecules such as tau on the microtubules that more strongly shield them from being severed by P60-katanin than by spastin. Consistent with this hypothesis, we found that axons depleted of tau show a greater propensity to branch, and that this is true whether or not the axons are also depleted of spastin. We propose that there are two modes by which microtubule severing is orchestrated during axonal branch formation, one based on the local concentration of spastin at branch sites and the other based on local detachment from microtubules of molecules such as tau that regulate the severing properties of P60-katanin.
Yu
Wenqian
W
Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PA 19129, USA.
Qiang
Liang
L
Solowska
Joanna M
JM
Karabay
Arzu
A
Korulu
Sirin
S
Baas
Peter W
PW
D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001369:Axons / Q000378:metabolism*; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D002478:Cells, Cultured; D015870:Gene Expression; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D000074201:Katanin; D051379:Mice; D008870:Microtubules / Q000378:metabolism*; D008959:Models, Neurological; D010641:Phenotype; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D000074181:Spastin; D014162:Transfection; D016875:tau Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism
D002352:Carrier Proteins; C489131:Mapt protein, rat; D034741:RNA, Small Interfering; D011993:Recombinant Fusion Proteins; C528700:ZFYVE26 protein, rat; C485184:enhanced green fluorescent protein; D016875:tau Proteins; D049452:Green Fluorescent Proteins; D000251:Adenosine Triphosphatases; D000074181:Spastin; D000074201:Katanin; C498515:Spast protein, mouse