Human CFEOM1 Mutations Attenuate KIF21A Autoinhibition and Cause Oculomotor Axon Stalling

• Published in: Neuron (Cambridge, Mass.) Vol. 82; no. 2; pp. 334 - 349
• Main Authors: Cheng, Long, Desai, Jigar, Miranda, Carlos J., Duncan, Jeremy S., Qiu, Weihong, Nugent, Alicia A., Kolpak, Adrianne L., Wu, Carrie C., Drokhlyansky, Eugene, Delisle, Michelle M., Chan, Wai-Man, Wei, Yan, Propst, Friedrich, Reck-Peterson, Samara L., Fritzsch, Bernd, Engle, Elizabeth C.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 16.04.2014; Elsevier Limited
• Subjects: Age Factors; Animals; Animals, Newborn; Axons - pathology; Axons - ultrastructure; Cell Count; Disease Models, Animal; Embryo, Mammalian; Experiments; Eye Diseases, Hereditary - genetics; Eye Diseases, Hereditary - pathology; Eye Diseases, Hereditary - physiopathology; Eye Movements - genetics; Eye Movements - physiology; Fibrosis - genetics; Fibrosis - pathology; Fibrosis - physiopathology; Gene Expression Regulation - genetics; Green Fluorescent Proteins - genetics; Green Fluorescent Proteins - metabolism; HEK293 Cells; Humans; Kinesins - genetics; Kinesins - metabolism; Mice; Mice, Transgenic; Microtubule-Associated Proteins - genetics; Microtubule-Associated Proteins - physiology; Motility; Mutation; Mutation - genetics; Neural Pathways - metabolism; Neural Pathways - pathology; Neural Pathways - ultrastructure; Neurons; Neurosciences; Ocular Motility Disorders - genetics; Ocular Motility Disorders - pathology; Ocular Motility Disorders - physiopathology; Oculomotor Nerve - pathology; Oculomotor Nerve - ultrastructure; Pathogenesis; Pathology; Proteins; Rodents

The ocular motility disorder “Congenital fibrosis of the extraocular muscles type 1” (CFEOM1) results from heterozygous mutations altering the motor and third coiled-coil stalk of the anterograde kinesin, KIF21A. We demonstrate that Kif21a knockin mice harboring the most common human mutation develo...