Association of the kinesin-binding domain of RanBP2 to KIF5B and KIF5C determines mitochondria localization and function - PubMed (original) (raw)

. 2007 Dec;8(12):1722-1735.

doi: 10.1111/j.1600-0854.2007.00647.x. Epub 2007 Sep 21.

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• PMID: 17887960
• DOI: 10.1111/j.1600-0854.2007.00647.x

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Association of the kinesin-binding domain of RanBP2 to KIF5B and KIF5C determines mitochondria localization and function

Kyoung-In Cho et al. Traffic. 2007 Dec.

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Abstract

The Ran-binding protein 2 (RanBP2) is a large mosaic protein with a pleiotropic role in cell function. Although the contribution of each partner and domain of RanBP2 to its biological functions are not understood, physiological deficits of RanBP2 downregulate glucose catabolism and energy homeostasis and lead to delocalization of mitochondria components in photosensory neurons. The kinesin-binding domain (KBD) of RanBP2 associates selectively in the central nervous system (CNS), and directly, with the ubiquitous and CNS-specific kinesins, KIF5B and KIF5C, respectively, but not with the highly homologous KIF5A. Here, we determine the molecular and biological bases of the selective interaction between RanBP2 and KIF5B/KIF5C. This interaction is conferred by a approximately 100-residue segment, comprising a portion of the coiled-coil and globular tail cargo-binding domains of KIF5B/KIF5C. A single residue conserved in KIF5B and KIF5C, but not KIF5A, confers KIF5-isotype-specific association with RanBP2. This interaction is also mediated by a conserved leucine-like heptad motif present in KIF5s and KBD of RanBP2. Selective inhibition of the interaction between KBD of RanBP2 and KIF5B/KIF5C in cell lines causes perinuclear clustering of mitochondria, but not of lysosomes, deficits in mitochondrial membrane potential and ultimately, cell shrinkage. Collectively, the data provide a rationale of the KIF5 subtype-specific interaction with RanBP2 and support a novel kinesin-dependent role of RanBP2 in mitochondria transport and function. The data also strengthen a model whereby the selection of a large array of cargoes for transport by a restricted number of motor proteins is mediated by adaptor proteins such as RanBP2.

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References

1. 1. Hirokawa N, Takemura R. Biochemical and molecular characterization of diseases linked to motor proteins. Trends Biochem Sci 2003;28:558-565.
2. 1. Duncan JE, Goldstein LS. The genetics of axonal transport and axonal transport disorders. PLoS Genet 2006;2:1275-1284.
3. 1. Caviston JP, Holzbaur EL. Microtubule motors at the intersection of trafficking and transport. Trends Cell Biol 2006;16:530-537.
4. 1. Hirokawa N, Takemura R. Molecular motors and mechanisms of directional transport in neurons. Nat Rev Neurosci 2005;6:201-214.
5. 1. Vale RD, Reese TS, Sheetz MP. Identification of a novel force-generating protein, kinesin, involved in microtubule-based motility. Cell 1985;42:39-50.

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