Structural basis for Arf6-MKLP1 complex formation on the Flemming body responsible for cytokinesis

Cytokinesis is the final stage of cell division, during which cells exhibit drastic morphological changes and remodeling of the cytoskeleton. The drastic shape changes and membrane fission event during cytokinesis entail local delivery and/or removal of membranes and specific proteins.

Arf6, which is a member of small GTPase family, is involved in cytokinesis by localizing to the Flemming body (the midbody). However, it remains unknown how Arf6 contributes to cytokinesis. Our collaboration team (KEK and Kyoto university) demonstrated that Arf6 directly interacts with mitotic kinesin-like protein 1 (MKLP1), which is known as a Flemming body-localizing protein essential for cytokinesis.

We determined the X-ray crystal structure of the Arf6-MKLP1 complex. The structure reveals that MKLP1 forms a homodimer flanked by two Arf6 molecules, forming a 2:2 heterotetramer containing an extended β-sheet that spans the entire heterotetramer, suitable for interaction with a concave membrane surface at the cleavage furrow. We showed 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 showed that the complex formation is required for completion of cytokinesis by structure-based mutagenesis and siRNA-mediated knockdowns. 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. This work will appear EMBO Journal on May 30, 2012.

More information:
Structural basis for Arf6-MKLP1 complex formation on the Flemming body responsible for cytokinesis.
Hisayoshi Makyio, Minako Ohgi, Tomomi Takei, Senye Takahashi, Hiroyuki Takatsu, Yohei Katoh, Ayako Hanai, Tomoko Ueda, Yasunori Kanaho, Yong Xie, Hye-Won Shin, Hironari Kamikubo, Mikio Kataoka, Masato Kawasaki, Ryuichi Kato, Soichi Wakatsuki and Kazuhisa Nakayama
EMBO Journal, Vol. 31, No. 11 (May 30, 2012).

Provided by Kyoto University