kinesins
Kinesins are tubulins (MIM.191130) molecular motors that function to transport organelles within cells and to move chromosomes along microtubules during cell division.
Members
| KNS1 (KNF5B) | KNS2A | KNS2B | ||||
| KIF1 | KIF2 | KIF2C | KIF3 | KIF4 | KIF5A | KIF5B |
Structure
Kinesins consist of 2 identical, approximately 110- to 120-kD heavy chains (KIF5A, KIF5B) and 2 identical, approximately 60- to 70-kD light chains (KNS2A).
The heavy chain contains 3 domains: a globular N-terminal motor domain, which converts the chemical energy of ATP into a motile force along microtubules in 1 fixed direction; a central alpha-helical rod domain, which enables the 2 heavy chains to dimerize; and a globular C-terminal domain, which interacts with light chains and possibly an organelle receptor.
Functions
Kinesins and kinesin-related proteins make up a large superfamily of molecular motors that transport cargoes such as vesicles, organelles (e.g. mitochondria, peroxisomes, lysosomes), protein complexes (e.g. elements of the cytoskeleton, virus particles), and mRNAs in a microtubule- and ATP-dependent manner in neuronal and non-neuronal cells.
In 2003, more than 45 kinesin superfamily proteins (KIFs) have been identified in the mouse and human genomes.
See also:
kinesin-related proteins (KRPs)
transport pathways mediated by kinesins
cargoes - cargo
proteins linking kinesin motors to cargoes
kinesins structure
binding partners of kinesins
kinesins-based human diseases (Pathology of kinesins)
Function
In sea urchin and mammalian cells, kinesins have been characterized as tetrameric proteins comprising 2 heavy chains (alpha chains) of approximately 120 kD and 2 light chains (beta chains) of approximately 70 kD. The alpha chains provide the tubulin binding site and the ATPase domains, whereas the beta chains are responsible for the specific attachment of the organelle to be moved by the kinesin tetramer. Kinesins transport their bound organelle to the plus end of the microtubule.
The heavy chain contains 3 domains: a globular N-terminal motor domain, which converts the chemical energy of ATP into a motile force along microtubules in 1 fixed direction; a central alpha-helical rod domain, which enables the 2 heavy chains to dimerize; and a globular C-terminal domain, which interacts with light chains and possibly an organelle receptor.
Kinesins are motor proteins that use the hydrolysis of ATP to do mechanical work. Most of these motors translocate cargo along the surface of the microtubule (MT). However, a subfamily of these motors (Kin-I kinesins) can destabilize MTs directly from their ends. This distinct ability makes their activity crucial during mitosis, when reordering of the MT cytoskeleton is most evident.
Pathology
defective transport of cell components
transport of pathogens
See also:
cell division
kinesins polymerization
mammalian kinesin mitotic centromere-associated kinesin (MCAK)
Kin-I kinesins
mitosis
Animations
Axonal transport: A movie from J Cell Biol
References
Carter NJ, Cross RA. Kinesin’s moonwalk. Curr Opin Cell Biol. 2006 Feb;18(1):61-7. PMID: #16361092#
Miki H, Okada Y, Hirokawa N. Analysis of the kinesin superfamily: insights into structure and function. Trends Cell Biol. 2005 Sep;15(9):467-76. PMID: #16084724#
Hirokawa N, Takemura R. Kinesin superfamily proteins and their various functions and dynamics. Exp Cell Res. 2004 Nov 15;301(1):50-9. PMID: #15501445#
Yildiz A, Selvin PR. Kinesin: walking, crawling or sliding along? Trends Cell Biol. 2005 Feb;15(2):112-20. PMID: #15695098#
Moore A, Wordeman L. The mechanism, function and regulation of depolymerizing kinesins during mitosis. Trends Cell Biol. 2004 Oct;14(10):537-46. PMID: #15450976#
Guzik BW, Goldstein LS. Microtubule-dependent transport in neurons: steps towards an understanding of regulation, function and dysfunction. Curr Opin Cell Biol. 2004 Aug;16(4):443-50. PMID: #15261678#
Gunawardena S, Goldstein LS. Cargo-carrying motor vehicles on the neuronal highway: transport pathways and neurodegenerative disease. J Neurobiol. 2004 Feb 5;58(2):258-71. PMID: #14704957#
Mandelkow E, Mandelkow EM. Kinesin motors and disease. Trends Cell Biol. 2002 Dec;12(12):585-91. PMID: #12495847#
Karcher RL, Deacon SW, Gelfand VI. Motor-cargo interactions : the key to transport specificity. Trends Cell Biol. 2002 Jan ;12(1):21-7. PMID : #11854006#
Goldstein LS. Molecular motors: from one motor many tails to one motor many tales. Trends Cell Biol. 2001 Dec;11(12):477-82. PMID: #11719052#
Goldstein LS. Kinesin molecular motors: transport pathways, receptors, and human disease. Proc Natl Acad Sci U S A. 2001 Jun 19;98(13):6999-7003. PMID: #11416178#
Manning BD, Snyder M. Drivers and passengers wanted! the role of kinesin-associated proteins. Trends Cell Biol. 2000 Jul;10(7):281-9. PMID: #10856931#