| Structural highlights
Function
[ARF6_MOUSE] GTP-binding protein involved in protein trafficking; regulates endocytic recycling and cytoskeleton remodeling. May modulate vesicle budding and uncoating within the Golgi apparatus Contributes to the regulation of dendritic branching and filopodia extension (By similarity). Involved in the regulation of dendritic spine development. [KIF23_HUMAN] Component of the centralspindlin complex that serves as a microtubule-dependent and Rho-mediated signaling required for the myosin contractile ring formation during the cell cycle cytokinesis. Essential for cytokinesis in Rho-mediated signaling. Required for the localization of ECT2 to the central spindle. Plus-end-directed motor enzyme that moves antiparallel microtubules in vitro.[1] [2]
Publication Abstract from PubMed
A small GTPase, Arf6, is involved in cytokinesis by localizing to the Flemming body (the midbody). However, it remains unknown how Arf6 contributes to cytokinesis. Here, we demonstrate that Arf6 directly interacts with mitotic kinesin-like protein 1 (MKLP1), a Flemming body-localizing protein essential for cytokinesis. The crystal structure of the Arf6-MKLP1 complex reveals that MKLP1 forms a homodimer flanked by two Arf6 molecules, forming a 2:2 heterotetramer containing an extended beta-sheet composed of 22 beta-strands that spans the entire heterotetramer, suitable for interaction with a concave membrane surface at the cleavage furrow. We show that, during cytokinesis, Arf6 is first accumulated around the cleavage furrow and, prior to abscission, recruited onto the Flemming body via interaction with MKLP1. We also show by structure-based mutagenesis and siRNA-mediated knockdowns that the complex formation is required for completion of cytokinesis. A model based on these results suggests that the Arf6-MKLP1 complex plays a crucial role in cytokinesis by connecting the microtubule bundle and membranes at the cleavage plane.
Structural basis for Arf6-MKLP1 complex formation on the Flemming body responsible for cytokinesis.,Makyio H, Ohgi M, Takei T, Takahashi S, Takatsu H, Katoh Y, Hanai A, Ueda T, Kanaho Y, Xie Y, Shin HW, Kamikubo H, Kataoka M, Kawasaki M, Kato R, Wakatsuki S, Nakayama K EMBO J. 2012 Apr 20. doi: 10.1038/emboj.2012.89. PMID:22522702[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Yuce O, Piekny A, Glotzer M. An ECT2-centralspindlin complex regulates the localization and function of RhoA. J Cell Biol. 2005 Aug 15;170(4):571-82. PMID:16103226 doi:10.1083/jcb.200501097
- ↑ Kamijo K, Ohara N, Abe M, Uchimura T, Hosoya H, Lee JS, Miki T. Dissecting the role of Rho-mediated signaling in contractile ring formation. Mol Biol Cell. 2006 Jan;17(1):43-55. Epub 2005 Oct 19. PMID:16236794 doi:10.1091/mbc.E05-06-0569
- ↑ Makyio H, Ohgi M, Takei T, Takahashi S, Takatsu H, Katoh Y, Hanai A, Ueda T, Kanaho Y, Xie Y, Shin HW, Kamikubo H, Kataoka M, Kawasaki M, Kato R, Wakatsuki S, Nakayama K. Structural basis for Arf6-MKLP1 complex formation on the Flemming body responsible for cytokinesis. EMBO J. 2012 Apr 20. doi: 10.1038/emboj.2012.89. PMID:22522702 doi:10.1038/emboj.2012.89
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