Home LiteratureArticle Details
PMID: 12015984 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Role of phosphatidylinositol(4,5)bisphosphate organization in membrane transport by the Unc104 kinesin motor.

Cell ·Vol. 109 ·No. 3 ·2002-05-03 ·Pages 347-58

Klopfenstein DR, Tomishige M, Stuurman N, Vale RD

Abstract

Unc104 (KIF1A) kinesin transports membrane vesicles along microtubules in lower and higher eukaryotes. Using an in vitro motility assay, we show that Unc104 uses a lipid binding pleckstrin homology (PH) domain to dock onto membrane cargo. Through its PH domain, Unc104 can transport phosphatidylinositol(4,5)bisphosphate (PtdIns(4,5)P2)-containing liposomes with similar properties to native vesicles. Interestingly, liposome movement by monomeric Unc104 motors shows a very steep dependence on PtdIns(4,5)P2 concentration (Hill coefficient of approximately 20), even though liposome binding is noncooperative. This switch-like transition for movement can be shifted to lower PtdIns(4,5)P2 concentrations by the addition of cholesterol/sphingomyelin or GM1 ganglioside/cholera toxin, conditions that produce raft-like behavior of Unc104 bound to lipid bilayers. These studies suggest that clustering of Unc104 in PtdIns(4,5)P2-containing rafts provides a trigger for membrane transport.

MeSH Terms
Amino Acid Sequence Animals Binding Sites Biological Transport Blood Proteins/chemistry,metabolism Caenorhabditis elegans/genetics Cell Membrane/drug effects,metabolism,physiology Dictyostelium Dose-Response Relationship, Drug In Vitro Techniques Kinesins/isolation & purification,metabolism Lipid Bilayers/metabolism Liposomes/metabolism Membrane Microdomains/metabolism Microtubules/physiology Models, Biological Nerve Tissue Proteins/isolation & purification,metabolism Phosphatidylinositol 4,5-Diphosphate/metabolism,physiology Phosphoproteins/chemistry,metabolism Sequence Homology, Amino Acid Transport Vesicles/physiology
Chemicals
Blood Proteins Lipid Bilayers Liposomes Nerve Tissue Proteins Phosphatidylinositol 4,5-Diphosphate Phosphoproteins platelet protein P47 Kinesins
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Klopfenstein Dieter R
Department of Cellular and Molecular Pharmacology, University of California, San Francisco, 513 Parnassus Avenue, 94143, USA.
Tomishige Michio
Stuurman Nico
Vale Ronald D
References (47)
47 references, click to expand
  1. Dynactin-dependent, dynein-driven vesicle transport in the absence of membrane proteins: a role for spectrin and acidic phospholipids.
    Mol Cell. 2001 Jan;7(1):173-83 PMID: 11172722
  2. Lipid rafts reconstituted in model membranes.
    Biophys J. 2001 Mar;80(3):1417-28 PMID: 11222302
  3. Regulation of molecular motor proteins.
    Int Rev Cytol. 2001;204:179-238 PMID: 11243595
  4. The effector domain of myristoylated alanine-rich C kinase substrate binds strongly to phosphatidylinositol 4,5-bisphosphate.
    J Biol Chem. 2001 Feb 16;276(7):5012-9 PMID: 11053422
  5. Direct visualization of the movement of the monomeric axonal transport motor UNC-104 along neuronal processes in living Caenorhabditis elegans.
    J Neurosci. 2001 Jun 1;21(11):3749-55 PMID: 11356862
  6. Switch-based mechanism of kinesin motors.
    Nature. 2001 May 24;411(6836):439-45 PMID: 11373668
  7. All kinesin superfamily protein, KIF, genes in mouse and human.
    Proc Natl Acad Sci U S A. 2001 Jun 19;98(13):7004-11 PMID: 11416179
  8. Roles of lipid rafts in membrane transport.
    Curr Opin Cell Biol. 2001 Aug;13(4):470-7 PMID: 11454454
  9. PI(4,5)P(2) regulation of surface membrane traffic.
    Curr Opin Cell Biol. 2001 Aug;13(4):493-9 PMID: 11454457
  10. New EMBO members' review: actin cytoskeleton regulation through modulation of PI(4,5)P(2) rafts.
    EMBO J. 2001 Aug 15;20(16):4332-6 PMID: 11500359
  11. KIF1D is a fast non-processive kinesin that demonstrates novel K-loop-dependent mechanochemistry.
    EMBO J. 2001 Sep 17;20(18):5101-13 PMID: 11566875
  12. KIFC3, a microtubule minus end-directed motor for the apical transport of annexin XIIIb-associated Triton-insoluble membranes.
    J Cell Biol. 2001 Oct 1;155(1):77-88 PMID: 11581287
  13. Molecular motors: from one motor many tails to one motor many tales.
    Trends Cell Biol. 2001 Dec;11(12):477-82 PMID: 11719052
  14. Tracking kinesin-driven movements with nanometre-scale precision.
    Nature. 1988 Feb 4;331(6155):450-3 PMID: 3123999
  15. Phosphoinositide content of erythrocyte membranes in cystic fibrosis.
    J Lab Clin Med. 1988 Mar;111(3):336-40 PMID: 2830355
  16. Movement of microtubules by single kinesin molecules.
    Nature. 1989 Nov 9;342(6246):154-8 PMID: 2530455
  17. Increased conversion of phosphatidylinositol to phosphatidylinositol phosphate in Dictyostelium cells expressing a mutated ras gene.
    Proc Natl Acad Sci U S A. 1990 Dec;87(23):9197-201 PMID: 2174555
  18. The UNC-104/KIF1 family of kinesins.
    Curr Opin Cell Biol. 2001 Feb;13(1):36-40 PMID: 11163131
  19. Myosin-X, a novel myosin with pleckstrin homology domains, associates with regions of dynamic actin.
    J Cell Sci. 2000 Oct;113 Pt 19:3439-51 PMID: 10984435
  20. Structural basis for high-affinity phosphoinositide binding by pleckstrin homology domains.
    Biochem Soc Trans. 1999 Aug;27(4):617-24 PMID: 10917653
  21. GAP43, MARCKS, and CAP23 modulate PI(4,5)P(2) at plasmalemmal rafts, and regulate cell cortex actin dynamics through a common mechanism.
    J Cell Biol. 2000 Jun 26;149(7):1455-72 PMID: 10871285
  22. The way things move: looking under the hood of molecular motor proteins.
    Science. 2000 Apr 7;288(5463):88-95 PMID: 10753125
  23. The C. elegans unc-104 gene encodes a putative kinesin heavy chain-like protein.
    Neuron. 1991 Jan;6(1):113-22 PMID: 1846075
  24. The role of gangliosides in the action of cholera toxin.
    Adv Exp Med Biol. 1976;71:205-14 PMID: 937148
  25. Reconstitution of membrane transport powered by a novel dimeric kinesin motor of the Unc104/KIF1A family purified from Dictyostelium.
    J Cell Biol. 1999 Nov 1;147(3):493-506 PMID: 10545495
  26. Cloning and expression of kinesins from the thermophilic fungus Thermomyces lanuginosus.
    Protein Sci. 1999 Dec;8(12):2705-10 PMID: 10631986
  27. Kinesin-related gene unc-104 is required for axonal transport of synaptic vesicles in C. elegans.
    Cell. 1991 May 31;65(5):837-47 PMID: 1710172
  28. Two activators of microtubule-based vesicle transport.
    J Cell Biol. 1991 Dec;115(5):1309-18 PMID: 1835460
  29. The neuron-specific kinesin superfamily protein KIF1A is a unique monomeric motor for anterograde axonal transport of synaptic vesicle precursors.
    Cell. 1995 Jun 2;81(5):769-80 PMID: 7539720
  30. Specificity and promiscuity in phosphoinositide binding by pleckstrin homology domains.
    J Biol Chem. 1998 Nov 13;273(46):30497-508 PMID: 9804818
  31. Determination of cholesterol at the low picomole level by nano-electrospray ionization tandem mass spectrometry.
    J Lipid Res. 1999 Jan;40(1):126-32 PMID: 9869658
  32. A processive single-headed motor: kinesin superfamily protein KIF1A.
    Science. 1999 Feb 19;283(5405):1152-7 PMID: 10024239
  33. Single-molecule behavior of monomeric and heteromeric kinesins.
    Biochemistry. 1999 Apr 27;38(17):5412-21 PMID: 10220328
  34. Motor and cargo interactions.
    Eur J Biochem. 1999 May;262(1):19-25 PMID: 10231359
  35. Localization and turnover of phosphatidylinositol 4,5-bisphosphate in caveolin-enriched membrane domains.
    J Biol Chem. 1996 Oct 25;271(43):26453-6 PMID: 8900109
  36. Functional rafts in cell membranes.
    Nature. 1997 Jun 5;387(6633):569-72 PMID: 9177342
  37. The directional preference of kinesin motors is specified by an element outside of the motor catalytic domain.
    Cell. 1997 Sep 5;90(5):959-66 PMID: 9298907
  38. Kinesin and dynein superfamily proteins and the mechanism of organelle transport.
    Science. 1998 Jan 23;279(5350):519-26 PMID: 9438838
  39. The design plan of kinesin motors.
    Annu Rev Cell Dev Biol. 1997;13:745-77 PMID: 9442886
  40. Binding of basic peptides to membranes produces lateral domains enriched in the acidic lipids phosphatidylserine and phosphatidylinositol 4,5-bisphosphate: an electrostatic model and experimental results.
    Biophys J. 1998 Feb;74(2 Pt 1):731-44 PMID: 9533686
  41. Defect in synaptic vesicle precursor transport and neuronal cell death in KIF1A motor protein-deficient mice.
    J Cell Biol. 1998 Apr 20;141(2):431-41 PMID: 9548721
  42. The synthesis and cellular roles of phosphatidylinositol 4,5-bisphosphate.
    Curr Opin Cell Biol. 1998 Apr;10(2):254-61 PMID: 9561850
  43. In vitro microtubule-based organelle transport in wild-type Dictyostelium and cells overexpressing a truncated dynein heavy chain.
    Cell Motil Cytoskeleton. 1998;40(3):304-14 PMID: 9678672
  44. GPI-anchored proteins are organized in submicron domains at the cell surface.
    Nature. 1998 Aug 20;394(6695):798-801 PMID: 9723621
  45. Sphingolipid-cholesterol rafts diffuse as small entities in the plasma membrane of mammalian cells.
    J Cell Biol. 2000 Mar 6;148(5):997-1008 PMID: 10704449
  46. Actin-dependent propulsion of endosomes and lysosomes by recruitment of N-WASP.
    J Cell Biol. 2000 Feb 7;148(3):519-30 PMID: 10662777
  47. Mechanism of the single-headed processivity: diffusional anchoring between the K-loop of kinesin and the C terminus of tubulin.
    Proc Natl Acad Sci U S A. 2000 Jan 18;97(2):640-5 PMID: 10639132
Article Info
Journal
Cell
Abbr.
Cell
ISSN
0092-8674
DOI
10.1016/s0092-8674(02)00708-0
Published
2002-05-03
Pages
347-58
Language
English
Region
United States
NLM ID
0413066
PMCID
PMC2851634
Subset
IM
Grants
Howard Hughes Medical Institute · United States
NIGMS NIH HHS · R01 GM038499 · United States
NIGMS NIH HHS · R01 GM038499-14 · United States
PHS HHS · NIH 38499 · United States
External Links
PubMed source DOI: 10.1016/s0092-8674(02)00708-0 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2