Interphase adhesion geometry is transmitted to an internal regulator for spindle orientation via caveolin-1.
Despite theoretical and physical studies implying that cell-extracellular matrix adhesion geometry governs the orientation of the cell division axis, the molecular mechanisms that translate interphase adhesion geometry to the mitotic spindle orientation remain elusive. Here, we show that the cellular edge retraction during mitotic cell rounding correlates with the spindle axis. At the onset of mitotic cell rounding, caveolin-1 is targeted to the retracting cortical region at the proximal end of retraction fibres, where ganglioside GM1-enriched membrane domains with clusters of caveola-like structures are formed in an integrin and RhoA-dependent manner. Furthermore, Gαi1-LGN-NuMA, a well-known regulatory complex of spindle orientation, is targeted to the caveolin-1-enriched cortical region to guide the spindle axis towards the cellular edge retraction. We propose that retraction-induced cortical heterogeneity of caveolin-1 during mitotic cell rounding sets the spindle orientation in the context of adhesion geometry.
Department of Cell Biology, Institute for Virus Research, Kyoto University, Sakyo-ku, Kyoto 606-8507, Japan.
Shigeru
S
Matsumura
Advanced ICT Research Institute Kobe, National Institute of Information and Communication Technology, Nishi-ku, Kobe 651-2492, Japan.|Department of Chemical and Biological Science, Japan Women's University, Bunkyo-ku, Tokyo 112-8681, Japan.
Tomoko
T
Kojidani
Department of Pathology and Biology of Diseases, Kyoto University, Kyoto 606-8315, Japan.|Innovative Techno-Hub for Integrated Medical Bio-Imaging, Kyoto University, Kyoto 606-8501, Japan.
Yuji
0000-0002-7532-1787
Y
Kamioka
Faculty of Information Science and Electrical Engineering, Kyushu University, Nishi-ku, Fukuoka 819-0395, Japan.
Seiichi
S
Uchida
Advanced ICT Research Institute Kobe, National Institute of Information and Communication Technology, Nishi-ku, Kobe 651-2492, Japan.
Tokuko
T
Haraguchi
Cell Architecture Laboratory, Structural Biology Center, National Institute of Genetics, Yata 1111, Mishima, Shizuoka 411-8540, Japan.
Akatsuki
0000-0003-4227-4811
A
Kimura
Department of Cell Biology, Institute for Virus Research, Kyoto University, Sakyo-ku, Kyoto 606-8507, Japan.
Fumiko
F
Toyoshima
D051242:Caveolin 1 / Q000378:metabolism*; D002448:Cell Adhesion; D002784:Cholesterol / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D019012:Integrin beta1 / Q000378:metabolism; D007399:Interphase; D021962:Membrane Microdomains / Q000378:metabolism; D008938:Mitosis; D008954:Models, Biological; D015398:Signal Transduction; D008941:Spindle Apparatus / Q000378:metabolism*; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
D051242:Caveolin 1; D019012:Integrin beta1; D002784:Cholesterol; D020742:rhoA GTP-Binding Protein