Effect of spastic paraplegia mutations in KIF5A kinesin on transport activity

Human Molecular Genetics
Bettina EbbingGünther Woehlke

Abstract

Hereditary spastic paraplegia (HSP) is a neurodegenerative disease caused by motoneuron degeneration. It is linked to at least 30 loci, among them SPG10, which causes dominant forms and originates in point mutations in the neuronal Kinesin-1 gene (KIF5A). Here, we investigate the motility of KIF5A and four HSP mutants. All mutations are single amino-acid exchanges and located in kinesin's motor or neck domain. The mutation in the neck (A361V) did not change the gliding properties in vitro, the others either reduced microtubule affinity or gliding velocity or both. In laser-trapping assays, none of the mutants moved more than a few steps along microtubules. Motility assays with mixtures of homodimeric wild-type, homodimeric mutant and heterodimeric wild-type/mutant motors revealed that only one mutant (N256S) reduces the gliding velocity at ratios present in heterozygous patients, whereas the others (K253N, R280C) do not. Attached to quantum dots as artificial cargo, mixtures involving N256S mutants produced slower cargo populations lagging behind in transport, whereas mixtures with the other mutants led to populations of quantum dots that rarely bound to microtubules. These differences indicate that the dominant inheritance of ...Continue Reading

References

Jan 1, 1991·Methods in Enzymology·A HymanT Mitchison
Sep 20, 1985·Journal of Molecular Biology·E M MandelkowU Rühl
Dec 15, 1993·Proceedings of the National Academy of Sciences of the United States of America·A J Hunt, J Howard
Mar 5, 1996·Proceedings of the National Academy of Sciences of the United States of America·C M CoppinR D Vale
Jul 24, 1997·Nature·M J Schnitzer, S M Block
Jul 24, 1997·Nature·W HuaJ Gelles
Jul 25, 1997·Cell·G WoehlkeR D Vale
Jan 1, 1997·Annual Review of Cell and Developmental Biology·R D Vale, R J Fletterick
Apr 29, 1998·The Journal of Cell Biology·W O Hancock, J Howard
Aug 31, 2000·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Y KanaiN Hirokawa
May 30, 2001·Current Opinion in Genetics & Development·G Casari, E Rugarli
Jun 20, 2001·Nature Reviews. Molecular Cell Biology·G Woehlke, M Schliwa
Jan 17, 2002·Current Opinion in Cell Biology·Jagesh V Shah, Don W Cleveland
Oct 2, 2002·American Journal of Human Genetics·Evan ReidDouglas A Marchuk
Jan 30, 2003·The EMBO Journal·Friederike SchäferGünther Woehlke
Mar 19, 2003·The Journal of Cell Biology·Anthony Brown
Apr 16, 2003·The Journal of Cell Biology·Chun-Hong XiaLawrence S B Goldstein
Apr 9, 2004·European Biophysics Journal : EBJ·D B HillG Holzwarth
Oct 7, 2004·Current Opinion in Neurobiology·Nobutaka Hirokawa, Reiko Takemura
Oct 23, 2004·Current Biology : CB·Robert M Gould, Scott T Brady
Feb 16, 2005·Nature Reviews. Neuroscience·Nobutaka Hirokawa, Reiko Takemura
Jun 25, 2005·Journal of Theoretical Biology·Gheorghe CraciunAvner Friedman
Jul 8, 2005·Molecular Biology of the Cell·Anthony BrownPeter Jung
Feb 21, 2006·Neurogenetics·Marcia A BlairPeter Hedera
May 23, 2006·Biophysical Journal·Johann JaudGünther Woehlke
Sep 29, 2006·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Aidong YuanRalph A Nixon
Apr 25, 2007·Experimental Cell Research·Devin M BarryMichael L Garcia

❮ Previous
Next ❯

Citations

Apr 3, 2012·Neurogenetics·Kathrin N KarleLudger Schöls
Jun 11, 2008·Current Neurology and Neuroscience Reports·Giovanni StevaninAlexis Brice
Oct 5, 2013·Trends in Cell Biology·Maria-Victoria HinckelmannFrédéric Saudou
May 29, 2012·The Journal of Biological Chemistry·Thomas EckertGünther Woehlke
May 1, 2012·Annual Review of Neuroscience·Craig Blackstone
Nov 23, 2010·Molecular Neurodegeneration·Lina Wang, Anthony Brown
Dec 29, 2012·PloS One·Thomas EckertGünther Woehlke
Jul 23, 2013·PloS One·Doan Tuong-Van LeGünther Woehlke
Dec 3, 2013·Bioinformatics·Hamidreza Khataee, Alan Wee-Chung Liew
Jan 15, 2011·Biomarkers : Biochemical Indicators of Exposure, Response, and Susceptibility to Chemicals·Brian C TookerPaul W Brandt-Rauf
Jun 24, 2014·Experimental Neurology·Temistocle Lo GiudiceAntonio Orlacchio
Oct 25, 2008·FEBS Letters·Kenji Kawaguchi
May 4, 2010·Trends in Neurosciences·Eran PerlsonErika L F Holzbaur
Dec 17, 2009·Trends in Cell Biology·Andrew F MacAskill, Josef T Kittler
Dec 1, 2014·Neuron·Catherine Diamante SorbaraMartin Kerschensteiner
Sep 10, 2008·Current Opinion in Neurobiology·Katharina E CoskerRosalind A Segal
Nov 7, 2014·Neuron·Sandra MadayErika L F Holzbaur
Feb 9, 2011·Neuropathology and Applied Neurobiology·L M DuffyA J Grierson
Jan 22, 2011·Biology of the Cell·Daniela SauAngelo Poletti
Sep 20, 2015·Human Molecular Genetics·Uirá S MeloSilvana Santos
Aug 19, 2015·Frontiers in Molecular Neuroscience·Arsalan AlizadehSoheila Karimi-Abdolrezaee
Jun 12, 2013·Translational Neuroscience·Xin-An LiuSathyanarayanan V Puthanveettil
Jun 22, 2011·Neuron·Eric A Schon, Serge Przedborski
May 5, 2012·Journal of the Neurological Sciences·Josef FinstererGiovanni Stevanin
Oct 28, 2018·Proceedings of the National Academy of Sciences of the United States of America·Mandira DuttaBiman Jana
Nov 19, 2013·The Journal of Biological Chemistry·Monika JoshiJohn S Allingham
Jan 19, 2018·European Journal of Human Genetics : EJHG·Sanna PuuseppKatrin Õunap
Dec 9, 2010·Nature Reviews. Neuroscience·Craig BlackstoneEvan Reid
Jan 31, 2013·Nature Reviews. Neuroscience·Stéphanie Millecamps, Jean-Pierre Julien
Feb 20, 2015·Journal of Clinical Neuromuscular Disease·Fabrizio RinaldiMassimiliano Filosto
Aug 14, 2019·Neurology. Genetics·Mattias AndréassonPer Svenningsson
Oct 17, 2019·Frontiers in Cellular Neuroscience·Dominik R GabrychMichael A Silverman

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.