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Molecular motor proteins of the kinesin superfamily proteins (KIFs): structure, cargo and disease.

Seog DH, Lee DH, Lee SK - J. Korean Med. Sci. (2004)

Bottom Line: Intracellular organelle transport is essential for morphogenesis and functioning of the cell.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology, College of Medicine, Inje University, Busan, Korea. daehyun@ijnc.inje.ac.kr

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.

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Related in: MedlinePlus

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.
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Figure 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.

Mentions: Although the interaction of motors and cargoes are only poorly understood, this is an area of rapid progress (8). Schliwa's group searched for functional KHC domains using KHC deletion mutant cDNAs expressed as transgenes and evaluated their ability to rescue the deduced growth rate of a KHC-deficient strain of Neurospora. In Neurospora, the tail coiled-coil domain (820-918 amino acids) of KHC is essential for targeting and secretion to small vesicles at the hyphal tip (9). Hirokawa's group showed that an AMPA (α-amino-3-hydroxy-5-methylisoxazole-4-propionate) receptor subunit-glutamate-receptor-interacting protein (GRIP1), one of the multi-PDZ-domain proteins at the synapse junction (10, 11), can directly interact with this tail coiled-coil domain of KHC and steer to dendrites as a motor for AMPA receptor (12) (Fig. 2A). The region between the sixth and seventh PDZ domain of GRIP1 binds to a region of KHC that overlaps the tail coiledcoil domain defined in Neurospora. This interaction was further confirmed by the observation that KHC and GRIP1 are present on the same vesicles within the dendrites of cultured hippocampus neurons and co-immunoprecitate in the vesicle fractions. In addition, both gene targeting and dominant negative experiments of KHC resulted in abnormal localization of GRIP1 and GluR2. In GRIP1 expressing neuronal cells, KIF5 carries GRIP1 associated vesicles towards dendrites; on the other hand, in cells expressing JSAP1/JIP3, KIF5 transports JSAP1 associated vesicles towards axons (12, 13). A simple explanation of this phenomenon is that binding proteins determine the general direction of the traffic and also that KIF family members can recognize multiple binding proteins or cargoes.


Molecular motor proteins of the kinesin superfamily proteins (KIFs): structure, cargo and disease.

Seog DH, Lee DH, Lee SK - J. Korean Med. Sci. (2004)

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.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2822243&req=5

Figure 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.
Mentions: Although the interaction of motors and cargoes are only poorly understood, this is an area of rapid progress (8). Schliwa's group searched for functional KHC domains using KHC deletion mutant cDNAs expressed as transgenes and evaluated their ability to rescue the deduced growth rate of a KHC-deficient strain of Neurospora. In Neurospora, the tail coiled-coil domain (820-918 amino acids) of KHC is essential for targeting and secretion to small vesicles at the hyphal tip (9). Hirokawa's group showed that an AMPA (α-amino-3-hydroxy-5-methylisoxazole-4-propionate) receptor subunit-glutamate-receptor-interacting protein (GRIP1), one of the multi-PDZ-domain proteins at the synapse junction (10, 11), can directly interact with this tail coiled-coil domain of KHC and steer to dendrites as a motor for AMPA receptor (12) (Fig. 2A). The region between the sixth and seventh PDZ domain of GRIP1 binds to a region of KHC that overlaps the tail coiledcoil domain defined in Neurospora. This interaction was further confirmed by the observation that KHC and GRIP1 are present on the same vesicles within the dendrites of cultured hippocampus neurons and co-immunoprecitate in the vesicle fractions. In addition, both gene targeting and dominant negative experiments of KHC resulted in abnormal localization of GRIP1 and GluR2. In GRIP1 expressing neuronal cells, KIF5 carries GRIP1 associated vesicles towards dendrites; on the other hand, in cells expressing JSAP1/JIP3, KIF5 transports JSAP1 associated vesicles towards axons (12, 13). A simple explanation of this phenomenon is that binding proteins determine the general direction of the traffic and also that KIF family members can recognize multiple binding proteins or cargoes.

Bottom Line: Intracellular organelle transport is essential for morphogenesis and functioning of the cell.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology, College of Medicine, Inje University, Busan, Korea. daehyun@ijnc.inje.ac.kr

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.

Show MeSH
Related in: MedlinePlus