A Neuron-Specific Isoform of Brain Ankyrin, 440 kD Ankyrin_B, As a Useful Tool in Neurobiology and Neurotoxicology

Abstract

Two isoforms of brain ankyrin, 440kD and 220kD ankyrin_B, are generated from the same gene by alternative splicing of pre-mRNA. The larger isoform shares the same NH₂-terminal and COOH-terminal domains as the smaller isoform and contains, in addition, a unique inserted domain of about 220kD in size. Both isoforms were expressed in primary neurons in a manner similar to that in vivo ; the larger isoform appeared first when axogenesis is actively conducted and the smaller isoform appeared later. 440kD ankyrin_B was localized in the axons of neurons both in vivo and in vitro, while the 220kD isoform was rather localized in the cell bodies and dendrites of neurons. The expression of 440kD ankyrin_B is intimately associated not only with neurite outgrowth but also with neurite retraction in neuronal cells, and is regulated at the mRNA level. Therefore, 440kD ankyrin_B is a specific and useful marker for neuritogenesis and is also a useful tool for investigating the effects of neurotoxic substances like methylmercury on the developing nervous system.