Tubulin cofactor B plays a role in the neuronal growth cone.
Tubulin cofactors, initially identified as alpha-, beta-tubulin folding proteins, are now believed to participate in the complex tubulin biogenesis and degradation routes, and thus to contribute to microtubule functional diversity and dynamics. However, a concrete role of tubulin cofactor B (TBCB) remains to be elucidated because this protein is not required for tubulin biogenesis, and it is apparently not essential for life in any of the organisms studied. In agreement with these data, here we show that TBCB localizes at the transition zone of the growth cones of growing neurites during neurogenesis where it plays a role in microtubule dynamics and plasticity. Gene silencing by means of small interfering RNA segments revealed that TBCB knockdown enhances axonal growth. In contrast, excess TBCB, a feature of giant axonal neuropathy, leads to microtubule depolymerization, growth cone retraction, and axonal damage followed by neuronal degeneration. These results provide an important insight into the understanding of the controlling mechanisms of growth cone microtubule dynamics.
Lopez-Fanarraga
M
M
Departamentos de Biología Molecular-Unidad Asociada al Centro de Investigaciones (CSIC), Facultad de Medicina, Universidad de Cantabria, Santander, Spain. fanarrag@unican.es
Carranza
G
G
Bellido
J
J
Kortazar
D
D
Villegas
J C
JC
Zabala
J C
JC
D000818:Animals; D000831:Animals, Newborn; D015152:Blotting, Northern / Q000379:methods; D001921:Brain / Q000166:cytology / Q000378:metabolism; D002478:Cells, Cultured; D004622:Embryo, Mammalian; D005786:Gene Expression Regulation / Q000187:drug effects; D020439:Growth Cones / Q000187:drug effects / Q000502:physiology*; D007150:Immunohistochemistry / Q000379:methods; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000502:physiology*; D008954:Models, Biological; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009447:Neuroblastoma; D009474:Neurons / Q000166:cytology* / Q000187:drug effects; D012333:RNA, Messenger / Q000096:biosynthesis; D034741:RNA, Small Interfering / Q000235:genetics / Q000494:pharmacology; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D014162:Transfection / Q000379:methods
D008869:Microtubule-Associated Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C518713:TBCB protein, mouse