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Amyotrophic Lateral Sclerosis; Rho Guanine Nucleotide Exchange Factor; Pleckstrin Homology Domain; Nuclear Localization Signal; Confocal Microscopy; Subcellular Fractionation
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Identification Of A Nuclear Localization Signal (Nls) Within The Pleckstrin Homology (Ph) Domain Of Rho Guanine Nucleotide Exchange Factor (Rgnef), Michael V. Tavolieri
Identification Of A Nuclear Localization Signal (Nls) Within The Pleckstrin Homology (Ph) Domain Of Rho Guanine Nucleotide Exchange Factor (Rgnef), Michael V. Tavolieri
Electronic Thesis and Dissertation Repository
Rho Guanine Nucleotide Exchange factor (RGNEF) is a 180 kDa protein which forms pathological neuronal cytoplasmic inclusions in degenerating spinal motor neurons in amyotrophic lateral sclerosis (ALS) and for which the gene (ARHGEF28) is mutated in a subset of cases. Despite having previously been shown to localize to the nucleus and to undergo a nuclear cytosolic shift in response to cellular injury, the mechanism of its nuclear import has yet to be elucidated. Here we use site-directed mutagenesis with a combination of subcellular fractionation and confocal microscopy to identify a functional nuclear localization signal (NLS) within the Pleckstrin …