Journal ArticleDOI
Heterozygous mutations of the kinesin KIF21A in congenital fibrosis of the extraocular muscles type 1 (CFEOM1)
Koki Yamada,Caroline Andrews,Wai-Man Chan,Craig A. McKeown,Adriano Magli,Teresa de Berardinis,Anat Loewenstein,Moshe Lazar,Michael O'Keefe,Robert D. Letson,Arnold London,Mark S. Ruttum,Naomichi Matsumoto,Nakamichi Saito,Lisa Morris,Monte A. Del Monte,Roger H. Johnson,Eiichiro Uyama,Willem A. Houtman,Berendina De Vries,Thomas J. Carlow,Blaine L. Hart,Nicolas Krawiecki,John M. Shoffner,Marlene C. Vogel,James A. Katowitz,Scott M. Goldstein,Alex V. Levin,Emin Cumhur Sener,Banu T. Öztürk,A. Nurten Akarsu,Michael C. Brodsky,Frank Hanisch,Robert P. Cruse,Alina A. Zubcov,Richard M. Robb,Peter Roggenkäemper,Irene Gottlob,Lionel Kowal,Ravi Battu,Elias I. Traboulsi,Piergiorgio Franceschini,Anna Newlin,Joseph L. Demer,Elizabeth C. Engle +44 more
TLDR
It is shown that individuals with CFEOM1 harbor heterozygous missense mutations in a kinesin motor protein encoded by Kif21A, highlighting an important new role for KIF21A and its stalk in the formation of the oculomotor axis.Abstract:
Congenital fibrosis of the extraocular muscles type 1 (CFEOM1; OMIM #135700) is an autosomal dominant strabismus disorder associated with defects of the oculomotor nerve. We show that individuals with CFEOM1 harbor heterozygous missense mutations in a kinesin motor protein encoded by KIF21A. We identified six different mutations in 44 of 45 probands. The primary mutational hotspots are in the stalk domain, highlighting an important new role for KIF21A and its stalk in the formation of the oculomotor axis.read more
Citations
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Kinesin superfamily motor proteins and intracellular transport
TL;DR: The mechanisms by which different kinesin recognize and bind to specific cargos, as well as how kinesins unload cargo and determine the direction of transport, have now been identified and open exciting new areas of kinesIn research.
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ALS: a disease of motor neurons and their nonneuronal neighbors.
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Molecular biology of amyotrophic lateral sclerosis: insights from genetics.
Piera Pasinelli,Robert H. Brown +1 more
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Molecular Motors in Neurons: Transport Mechanisms and Roles in Brain Function, Development, and Disease
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Axonal transport: cargo-specific mechanisms of motility and regulation
TL;DR: An overview of axonal transport pathways is provided and their role in neuronal function is discussed and Retrograde transport, which plays a major role in neurotrophic and injury response signaling, is discussed.
References
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Journal ArticleDOI
Charcot-Marie-Tooth Disease Type 2A Caused by Mutation in a Microtubule Motor KIF1Bβ
Chunjie Zhao,Junko Takita,Yosuke Tanaka,Mitsutoshi Setou,Terunaga Nakagawa,Sen Takeda,Hongwei Yang,Sumio Terada,Takao Nakata,Yosuke Takei,Masaaki Saito,Shoji Tsuji,Yasuhide Hayashi,Nobutaka Hirokawa +13 more
TL;DR: It is shown that CMT2A patients contain a loss-of-function mutation in the motor domain of the KIF1B gene, clear indication that defects in axonal transport due to a mutated motor protein can underlie human peripheral neuropathy.
Journal ArticleDOI
All kinesin superfamily protein, KIF, genes in mouse and human
TL;DR: The identification and classification of all kinesin superfamily proteins (KIFs) in mouse and human genome transcripts are reported to set the foundation of KIF and intracellular transport research.
Journal ArticleDOI
A Kinesin Heavy Chain (KIF5A) Mutation in Hereditary Spastic Paraplegia (SPG10)
Evan Reid,Mark T. Kloos,Allison E. Ashley-Koch,Lori Hughes,Simon Bevan,Ingrid K. Svenson,Felicia L. Graham,Perry C. Gaskell,A M Dearlove,Margaret A. Pericak-Vance,David C. Rubinsztein,Douglas A. Marchuk +11 more
TL;DR: This finding suggests that the underlying pathology of SPG10 and possibly of other forms of hereditary spastic paraplegia may involve perturbation of neuronal anterograde (or retrograde) axoplasmic flow, leading to axonal degeneration, especially in the longest axons of the central nervous system.
Journal ArticleDOI
Oculomotor nerve and muscle abnormalities in congenital fibrosis of the extraocular muscles.
Elizabeth C. Engle,Boyan C. Goumnerov,Craig A. McKeown,Martha P. Schatz,Donald R. Johns,John D. Porter,Alan H. Beggs +6 more
TL;DR: Evidence is presented that congenital fibrosis of theextraocular muscles results from an abnormality in the development of the extraocular muscle lower motor neuron system, suggesting that the muscle pathology extends beyond the muscles innervated by the superior division of cranial nerve III.
Journal ArticleDOI
Novel Dendritic Kinesin Sorting Identified by Different Process Targeting of Two Related Kinesins: KIF21A and KIF21B
TL;DR: It is suggested that a novel kinesin sorting mechanism is used by neurons to localize KIF21B protein to dendrites since its mRNA is restricted to the cell body.
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