@article {2931,
	title = {A laminopathic mutation disrupting lamin filament assembly causes disease-like phenotypes in Caenorhabditis elegans.},
	journal = {Mol Biol Cell},
	volume = {22},
	number = {15},
	year = {2011},
	month = {2011 Aug 1},
	pages = {2716-28},
	abstract = {Mutations in the human LMNA gene underlie many laminopathic diseases, including Emery-Dreifuss muscular dystrophy (EDMD); however, a mechanistic link between the effect of mutations on lamin filament assembly and disease phenotypes has not been established. We studied the ΔK46 Caenorhabditis elegans lamin mutant, corresponding to EDMD-linked ΔK32 in human lamins A and C. Cryo-electron tomography of lamin ΔK46 filaments in vitro revealed alterations in the lateral assembly of dimeric head-to-tail polymers, which causes abnormal organization of tetrameric protofilaments. Green fluorescent protein (GFP):ΔK46 lamin expressed in C. elegans was found in nuclear aggregates in postembryonic stages along with LEM-2. GFP:ΔK46 also caused mislocalization of emerin away from the nuclear periphery, consistent with a decreased ability of purified emerin to associate with lamin ΔK46 filaments in vitro. GFP:ΔK46 animals had motility defects and muscle structure abnormalities. These results show that changes in lamin filament structure can translate into disease-like phenotypes via altering the localization of nuclear lamina proteins, and suggest a model for how the ΔK32 lamin mutation may cause EDMD in humans.},
	keywords = {Amino Acid Sequence, Animals, Caenorhabditis elegans, Cloning, Molecular, Cryoelectron Microscopy, Cytoskeleton, Disease Models, Animal, Escherichia coli, Genetic Association Studies, Green Fluorescent Proteins, Humans, Lamin Type A, Membrane Proteins, Molecular Sequence Data, Movement, Muscles, Muscular Dystrophy, Emery-Dreifuss, Mutation, Nuclear Lamina, Nuclear Proteins, Phenotype, Plasmids, Recombinant Proteins, Transformation, Bacterial},
	issn = {1939-4586},
	doi = {10.1091/mbc.E11-01-0064},
	author = {Bank, Erin M and Ben-Harush, Kfir and Wiesel-Motiuk, Naama and Barkan, Rachel and Feinstein, Naomi and Lotan, Oren and Medalia, Ohad and Gruenbaum, Yosef}
}
