J Korean Med Sci.  2004 Feb;19(1):1-7. 10.3346/jkms.2004.19.1.1.

Molecular Motor Proteins of the Kinesin Superfamily Proteins (KIFs): Structure, Cargo and Disease

• Seog DH
• Lee DH
• Lee SK

• KMID: 1785685
• DOI: http://doi.org/10.3346/jkms.2004.19.1.1

Abstract

Intracellular organelle transport is essential for morphogenesis and functioning of the cell. 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. Until now, more than 45 kinesin superfamily proteins (KIFs) have been identified in the mouse and human genomes. Elucidating the transport pathways mediated by kinesins, the identities of the cargoes moved, and the nature of the proteins that link kinesin motors to cargoes are areas of intense investigation. This review focuses on the structure, the binding partners of kinesins and kinesin-based human diseases.

Keyword

Kinesin; Molecular Motors; Adaptor Proteins; Microtubules

MeSH Terms

Adenosine Triphosphate/metabolism
Alzheimer Disease/metabolism
Animals
Biological Transport
Cytoplasm/metabolism
Diabetes Mellitus/metabolism
Human
Kinesin/*chemistry/*metabolism
Mice
Microtubule-Associated Proteins/chemistry
Microtubules/metabolism
Models, Biological
Neurons/metabolism
Protein Binding
Support, Non-U.S. Gov't

Figure

• 

  Fig. 1 Movement of kinesin along a microtubule. At the start of the cycle, the ATP bounded head binds to the microtubule. ATP hydrolysis in the first head and exchange of ATP for ADP in the second head pulls the first head off the microtubule and moves the first head along the microtubule. With the cycle repeats, kinesin has moves the plus end of the microtubule.

• 

  Fig. 2 Schematic diagrams of the involvement of KIF5, KIF17, KIF3 and KIF13A in vesicle transport. (A) A model of the AMPA (α-amino-3-hydroxy-5-methylisoxazole-4-propionate) receptor transporting machinery. A subunit of AMPA receptor-GluR2-interacting protein (GRIP1)-can directly interact with and steer KHCs to dendrites. (B) A model of the NMDA receptor transporting machinery. Cargoes containing NR2B are transported by KIF17, and the mLin-10 binding domain is necessary for this function of KIF17. (C) A model of the involvement of KIF3 in vesicle transport. The KIF3 complex conveys fodrin-associated vesicles through a direct interaction with KAP3. (D) A model of the involvement of KIF13A in vesicle transport. The relationship between microtubule, KIF13A, and the AP-1 complex is shown. The AP-1 complex links transmembrane receptors (in this case M6PR) on the membrane to KIF13A through interaction between the AP-1 complex and the KIF13A tail domain.

• 

  Fig. 3 The binding partners of KIFs. Biochemical observations suggest that cargoes of motor proteins seem to be vesicles that possess specific functional marker molecules. The KIF3 complex conveys fodrin-associated vesicles through direct interaction of KAP3 with fodrin and plays a role in neurite elongation. KIF5 transports APP containing vesicles in the axon and conveys AMPA receptor containing vesicles in the dendrite. KIF5 is committed to carrying multiple cargoes to the axon or dendrite. KIF13A transports M6PR containing vesicles through direct interaction with the AP-1 complex from the TGN to the plasma membrane. KIF17 conveys NR2B-containing vesicles via a complex of mLin-10, mLin-2 and mLin-7, and may modulate the efficacy of synaptic transmission.

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