Journal
SCIENTIFIC REPORTS
Volume 5, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/srep08389
Keywords
-
Categories
Funding
- Canadian Institute for Health Research (CIHR)
- Canadian Cancer Society Research Institute (CSRI)
- Ferry Dow Endowment for IBD Research
Ask authors/readers for more resources
Cells must divide strictly along a plane to form an epithelial layer parallel to the basal lamina. The axis of cell division is primarily governed by the orientation of the mitotic spindle and spindle misorientation pathways have been implicated in cancer initiation. While beta 1-Integrin and the Dynein/Dynactin complex are known to be involved, the pathways linking these complexes in positioning mitotic spindles relative to the basal cortex and extracellular matrix remain to be elucidated. Here, we show that Integrin-Linked Kinase ( ILK) and alpha-Parvin regulate mitotic spindle orientation by linking Dynactin-1 and Dynactin-2 subunits of the Dynein/Dynactin complex to Integrin receptors at the basal cortex of mitotic cells. ILK and alpha-Parvin are required for spindle orientation. ILK interacts with Dynactin-1 and Dynactin-2 and ILK siRNA attenuates Dynactin-2 localization to the basal cortex. Furthermore we show that Dynactin-2 can no longer colocalize or interact with Integrins when ILK is absent, suggesting mechanistically that ILK is acting as a linking protein. Finally we demonstrate that spindle orientation and cell proliferation are disrupted in intestinal epithelial cells in vivo using tissue-specific ILK knockout mice. These data demonstrate that ILK is a linker between Integrin receptors and the Dynactin complex to regulate mitotic spindle orientation.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available