Caltubin, a novel molluscan tubulin-interacting protein, promotes axonal growth and attenuates axonal degeneration of rodent neurons.
Axotomized central neurons of most invertebrate species demonstrate a strong regenerative capacity, and as such may provide valuable molecular insights and new tools to promote axonal regeneration in injured mammalian neurons. In this study, we identified a novel molluscan protein, caltubin, ubiquitously expressed in central neurons of Lymnaea stagnalis and locally synthesized in regenerating neurites. Reduction of caltubin levels by gene silencing inhibits the outgrowth and regenerative ability of adult Lymnaea neurons and decreases local α- and β-tubulin levels in neurites. Caltubin binds to α- and/or β-tubulin in both Lymnaea and rodent neurons. Expression of caltubin in PC12 cells and mouse cortical neurons promotes NGF-induced axonal outgrowth and attenuates axonal retraction after injury. This is the first study illustrating that a xenoprotein can enhance outgrowth and prevent degeneration of injured mammalian neurons. These results may open up new avenues in molecular repair strategies through the insertion of molecular components of invertebrate regenerative pathways into mammalian neurons.
Department of Physiology, University of Toronto, Toronto, Ontario M5S 1A8, Canada.
Nasrin
N
Nejatbakhsh
Cong-Hui
CH
Guo
Tom Z
TZ
Lu
Lin
L
Pei
August B
AB
Smit
Hong-Shuo
HS
Sun
Ronald E
RE
van Kesteren
Zhong-Ping
ZP
Feng
D000818:Animals; D001369:Axons / Q000187:drug effects / Q000378:metabolism*; D019771:Axotomy / Q000379:methods; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D004195:Disease Models, Animal; D020832:EF Hand Motifs / Q000235:genetics / Q000502:physiology; D017952:Ganglia, Invertebrate / Q000166:cytology; D005786:Gene Expression Regulation / Q000187:drug effects; D049452:Green Fluorescent Proteins / Q000235:genetics; D047468:Immunoprecipitation; D008195:Lymnaea; D051379:Mice; D018613:Microscopy, Confocal; D009410:Nerve Degeneration / Q000517:prevention & control*; D020932:Nerve Growth Factor / Q000494:pharmacology; D009416:Nerve Regeneration / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000166:cytology* / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000494:pharmacology; D051381:Rats; D013947:Thymosin / Q000378:metabolism; D014162:Transfection / Q000379:methods; D014404:Tubulin / Q000235:genetics / Q000378:metabolism*
D002135:Calcium-Binding Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D014404:Tubulin; C568626:caltubin, Lymnaea stagnalis; D049452:Green Fluorescent Proteins; D013947:Thymosin; D020932:Nerve Growth Factor