title: zRICH, a protein induced during optic nerve regeneration in zebrafish, promotes neuritogenesis and interacts with tubulin.
abstract: Mammals do not regenerate axons in their central nervous system (CNS) spontaneously. This phenomenon is the cause of numerous medical conditions after damage to nerve fibers in the CNS of humans. The study of the mechanisms of nerve regeneration in other vertebrate animals able to spontaneously regenerate axons in their CNS is essential for understanding nerve regeneration from a scientific point of view, and for developing therapeutic approaches to enhance nerve regeneration in the CNS of humans. RICH proteins are a novel group of proteins implicated in nerve regeneration in the CNS of teleost fish, yet their mechanisms of action are not well understood. A number of mutant versions of the zebrafish RICH (zRICH) protein were generated and characterized at biochemical and cellular levels in our laboratory. With the aim of understanding the effects of RICH proteins in neuronal axon outgrowth, stable transfectants derived from the neuronal model PC12 cell line expressing zRICH Wild-Type or mutant versions of zRICH were studied. Results from differentiation experiments suggest that RICH proteins enhance neuronal plasticity by facilitating neurite branching. Biochemical co-purification results have demonstrated that zRICH binds to the cytoskeletal protein tubulin. The central domain of the protein is sufficient for tubulin binding, but a mutant version of the protein lacking the terminal domains, which cannot bind to the plasma membrane, was not able to enhance neurite branching. RICH proteins may facilitate axon regeneration by regulating the axonal cytoskeleton and facilitating the formation of new neurite branches.
authors.affiliation: Department of Biological and Health Sciences, Texas A&M University-Kingsville, Kingsville, TX 78363, United States.
authors.forename: Satya S
authors.initials: SS
authors.lastname: Pathi
authors.forename: Soumia
authors.initials: S
authors.lastname: Jose
authors.forename: Suman
authors.initials: S
authors.lastname: Govindaraju
authors.forename: Juan A
authors.initials: JA
authors.lastname: Conde
authors.forename: Hannah E
authors.initials: HE
authors.lastname: Romo
authors.forename: Karthik R
authors.initials: KR
authors.lastname: Chamakura
authors.forename: Cheryl J
authors.initials: CJ
authors.lastname: Claunch
authors.forename: Ana
authors.initials: A
authors.lastname: Benito-Martín
authors.forename: Madhavi
authors.initials: M
authors.lastname: Challa-Malladi
authors.forename: Maribel
authors.initials: M
authors.lastname: González-García
authors.forename: Rafael P
authors.initials: RP
authors.lastname: Ballestero
mesh_terms: D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D009416:Nerve Regeneration / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D055495:Neurogenesis / Q000502:physiology*; D009900:Optic Nerve / Q000378:metabolism*; D016716:PC12 Cells; D010727:Phosphoric Diester Hydrolases; D051381:Rats; D014162:Transfection; D014404:Tubulin / Q000378:metabolism*; D015027:Zebrafish / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000378:metabolism*
chemical_list: D009419:Nerve Tissue Proteins; D014404:Tubulin; D029961:Zebrafish Proteins; D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases; D010727:Phosphoric Diester Hydrolases; C577162:cnp protein, zebrafish