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PMID:20479469
| Citation |
Rodriguez-Fraticelli, AE, Vergarajauregui, S, Eastburn, DJ, Datta, A, Alonso, MA, Mostov, K and Martín-Belmonte, F (2010) The Cdc42 GEF Intersectin 2 controls mitotic spindle orientation to form the lumen during epithelial morphogenesis. J. Cell Biol. 189:725-38 |
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| Abstract |
Epithelial organs are made of tubes and cavities lined by a monolayer of polarized cells that enclose the central lumen. Lumen formation is a crucial step in the formation of epithelial organs. The Rho guanosine triphosphatase (GTPase) Cdc42, which is a master regulator of cell polarity, regulates the formation of the central lumen in epithelial morphogenesis. However, how Cdc42 is regulated during this process is still poorly understood. Guanine nucleotide exchange factors (GEFs) control the activation of small GTPases. Using the three-dimensional Madin-Darby canine kidney model, we have identified a Cdc42-specific GEF, Intersectin 2 (ITSN2), which localizes to the centrosomes and regulates Cdc42 activation during epithelial morphogenesis. Silencing of either Cdc42 or ITSN2 disrupts the correct orientation of the mitotic spindle and normal lumen formation, suggesting a direct relationship between these processes. Furthermore, we demonstrated this direct relationship using LGN, a component of the machinery for mitotic spindle positioning, whose disruption also results in lumen formation defects. |
| Links |
PubMed PMC2872911 Online version:10.1083/jcb.201002047 |
| Keywords |
Adaptor Proteins, Vesicular Transport/metabolism; Animals; Cell Cycle; Cells, Cultured; Dogs; Epithelial Cells/cytology; Epithelial Cells/metabolism; Epithelial Cells/ultrastructure; Guanine Nucleotide Exchange Factors/metabolism; Mitotic Spindle Apparatus/metabolism; Mitotic Spindle Apparatus/ultrastructure; Morphogenesis/physiology; RNA Interference; Signal Transduction; Tubulin/analysis; cdc42 GTP-Binding Protein/metabolism |
| edit table |
Significance
Annotations
| Gene product | Qualifier | GO Term | Evidence Code | with/from | Aspect | Extension | Notes | Status |
|---|---|---|---|---|---|---|---|---|
|
part_of |
GO:0005813: centrosome |
ECO:0000314: direct assay evidence used in manual assertion |
C |
Seeded From UniProt |
complete | |||
| GO:0005813: centrosome |
ECO:0000314: |
C |
Figure 2B. |
complete | ||||
See also
References
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