Expression of Neuronal Kinesin Heavy Chain Is Developmentally Regulated in the Central Nervous System of the Rat

Vignali, Giulia; Lizier, Carlotta; Sprocati, M. T.; Sirtori, Cesare R.; Battaglia, Giorgio; Navone, Francesca

doi:10.1046/j.1471-4159.1997.69051840.x

Cited by 15 publications

(14 citation statements)

References 30 publications

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“…These neurons are "regenerating," even in the adult brain (Paxinos, 1995). We observed high expression of KIF5B in cultured hippocampal and spinal cord neurons (data not shown), and previous studies have revealed that the expression of kinesin was upregulated in the developing rat CNS (Vignali et al, 1997) and disruption of KIF5B using antisense oligonucleotides reduced the neurite length and inhibited vesicle transport in cultured hippocampal neurons (Ferreira et al, 1992). These findings collectively suggest that the expression of KIF5B is highly upregulated in neurons at the stage of axonal elongation.…”

Section: Roles Of the Three Kif5s In Neuronssupporting

confidence: 85%

“…KIF5A was expressed evenly among neurons, with similar pattern of distribution to its human homolog, nKHC (Navone et al, 1992;Niclas et al, 1994;Vignali et al, 1996Vignali et al, , 1997. On the other hand, expression of KIF5C was highly upregulated, especially in mature lower motor neurons, indicating its important roles in the maintenance of motor neurons rather than in their formation.…”

Section: Roles Of the Three Kif5s In Neuronsmentioning

confidence: 84%

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KIF5C, a Novel Neuronal Kinesin Enriched in Motor Neurons

et al. 2000

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Kinesin superfamily proteins (KIFs) are the molecular motors conveying cargos along microtubules. KIF5s, the heavy chains of conventional kinesin (KHC), are originally identified members of KIFs, and neuronal KIF5A and ubiquitous KIF5B have been identified so far. In the present work, we cloned a novel member of KIF5, KIF5C, and generated specific antibodies against three KIF5s to investigate their distribution and functions. KIF5A showed pan-neuronal distribution in the nervous system. KIF5B showed a glial cell distribution pattern in general; however, interestingly, its expression was strongly upregulated in axonelongating neurons, such as olfactory primary neurons and mossy fibers. KIF5C was also a neuronal KIF5 like KIF5A but was highly expressed in lower motor neurons in 2-week-old or older mice, suggesting its important roles in the maintenance of motor neurons rather than in their formation, such as axonal elongation. Because a large part of KIF5s in adult motor neurons were expected to be KIF5C, we generated mice lacking the kif5C gene to investigate the functions of KIF5C in neurons in living animals. The mutant mice showed smaller brain size but were viable and did not show gross changes in the nervous system. Closer examinations revealed the relative loss of motor neurons to sensory neurons. Because three KIF5s showed high similarity in the amino acid sequence, could rescue the KIF5B mutant cells, and could form heterodimers, we think that there are functional redundancy among the three KIF5s and that KIF5A and KIF5B prevented the KIF5C null mice from the severe phenotype.Key words: kinesin; KIFs; KIF5A; KIF5B; KIF5C; motor neuron; axonal transport; brain; cloning; gene targeting Kinesin superfamily proteins are the molecular motors acting in the microtubule-based motilities of organelles in eukaryotic cells. More than 10 members of the murine kinesin superfamily proteins (KIFs) have been identified in the nervous system (Aizawa et al

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Section: Roles Of the Three Kif5s In Neuronssupporting

confidence: 85%

Section: Roles Of the Three Kif5s In Neuronsmentioning

confidence: 84%

KIF5C, a Novel Neuronal Kinesin Enriched in Motor Neurons

et al. 2000

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“…The age of vulnerability is associated with a period of motor learning in humans and corresponds to a developmental stage of high synaptic plasticity in primate (71) and rodent (72) neostriatum. In rat brain, kinesin-I is enriched in elongating neurites and growth cones (73,74). Similarly, we found enrichment of both kinesin and torsinA in growth cones of cultured rat cortical neurons.…”

Section: Nx(t/s) Asnsupporting

confidence: 72%

The Early Onset Dystonia Protein TorsinA Interacts with Kinesin Light Chain 1

Kamm

Boston

Hewett

et al. 2004

Journal of Biological Chemistry

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Early onset dystonia is a movement disorder caused by loss of a glutamic acid residue (Glu 302/303 ) in the carboxyl-terminal portion of the AAA ؉ protein, torsinA. We identified the light chain subunit (KLC1) of kinesin-I as an interacting partner for torsinA, with binding occurring between the tetratricopeptide repeat domain of KLC1 and the carboxyl-terminal region of torsinA. Coimmunoprecipitation analysis demonstrated that wildtype torsinA and kinesin-I form a complex in vivo. In cultured cortical neurons, both proteins co-localized along processes with enrichment at growth cones. Wildtype torsinA expressed in CAD cells co-localized with endogenous KLC1 at the distal end of processes, whereas mutant torsinA remained confined to the cell body. Subcellular fractionation of adult rat brain revealed torsinA and KLC associated with cofractionating membranes, and both proteins were co-immunoprecipitated after cross-linking cytoplasmically oriented proteins on isolated rat brain membranes. These studies suggest that wild-type torsinA undergoes anterograde transport along microtubules mediated by kinesin and may act as a molecular chaperone regulating kinesin activity and/or cargo binding.

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“…Although the precise significance of this heterogeneity in conventional kinesin subunits from brain is unknown, it likely reflects functional differences (13). Supporting this idea, kinesin-1s showed significant differences in their tissue distribution (25,26), developmental expression profiles (43), and transport rates (18), and specific KLC isoform variants are found in association to different MBOs (11,12,44). From these observations, it became apparent that determining the precise composition of conventional kinesin from brain represented a critical step toward an understanding of mechanisms underlying the targeting of conventional kinesin to different MBOs.…”

Section: Discussionmentioning

confidence: 97%

Conventional Kinesin Holoenzymes Are Composed of Heavy and Light Chain Homodimers

et al. 2008

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Conventional kinesin is a major microtubule-based motor protein responsible for anterograde transport of various membrane-bounded organelles (MBO) along axons. Structurally, this molecular motor protein is a tetrameric complex composed of two heavy (kinesin-1) chains and two light chain (KLC) subunits. The products of three kinesin-1 (kinesin-1A, -1B, and -1C, formerly KIF5A, -B, and -C) and two KLC (KLC1, KLC2) genes are expressed in mammalian nervous tissue, but the functional significance of this subunit heterogeneity remains unknown. In this work, we examine all possible combinations among conventional kinesin subunits in brain tissue. In sharp contrast with previous reports, immunoprecipitation experiments here demonstrate that conventional kinesin holoenzymes are formed of kinesin-1 homodimers. Similar experiments confirmed previous findings of KLC homodimerization. Additionally, no specificity was found in the interaction between kinesin-1s and KLCs, suggesting the existence of six variant forms of conventional kinesin, as defined by their gene product composition. Subcellular fractionation studies indicate that such variants associate with biochemically different MBOs and further suggest a role of kinesin-1s in the targeting of conventional kinesin holoenzymes to specific MBO cargoes. Taken together, our data address the combination of subunits that characterize endogenous conventional kinesin. Findings on the composition and subunit organization of conventional kinesin as described here provide a molecular basis for the regulation of axonal transport and delivery of selected MBOs to discrete subcellular locations.Molecular motors of the kinesin and dynein superfamilies are responsible for microtubule-(MT-) based motility in cells. Approximately 40−45 kinesin-related polypeptides have been identified in mouse and human (1), with 25 or more being expressed in the developing nervous system (2). From these, conventional kinesin is the most abundant kinesin family member in the adult nervous system (3). Biochemical (4) and electron microscopic studies (5) indicated that the native conventional kinesin holoenzyme exists as a tetramer consisting of two kinesin light chain (KLCs) 1 and two kinesin heavy chain (kinesin-1, KHC, KIF5s) subunits (6). † This work was supported by grants from the Huntington's Disease Society of America (HDSA) and ALSA (to G.M.), grants from NINDS (NS23868, NS23320, NS41170 and NS43408), MDA, and ALSA (to S.T.B.), and the Fitz-Thyssen Foundation and DFG (to S.K.).* To whom correspondence should be addressed. Phone: (312) 996−6791. Fax: (312) 413−0354. E-mail: gmorfini@uic.edu.. ‡ These authors contributed equally to this paper. § University of Illinois at Chicago. ∥ University of Heidelberg.1 Abbreviations: KHC, kinesin heavy chain; KLC, kinesin light chain; TR, tandem repeats; PIPES, 1,4-piperazinediethanesulfonic acid; HEPES, N-(2-hydroxyethyl)piperazine-N′-2-ethanesulfonic acid; AMP-PNP, adenosine 5′-(β,γ-imino)triphosphate; GST, glutathione Stransferase; SDS-PAGE, sodium d...

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Expression of Neuronal Kinesin Heavy Chain Is Developmentally Regulated in the Central Nervous System of the Rat

Cited by 15 publications

References 30 publications

KIF5C, a Novel Neuronal Kinesin Enriched in Motor Neurons

KIF5C, a Novel Neuronal Kinesin Enriched in Motor Neurons

The Early Onset Dystonia Protein TorsinA Interacts with Kinesin Light Chain 1

Conventional Kinesin Holoenzymes Are Composed of Heavy and Light Chain Homodimers

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