(Entry #3 for the week of science)
Perhaps the most fundamental aspect of migration of any kind is, how do you know which way to point yourself? Heck, this isn’t just about migration, it’s about how something is oriented in its immediate environment. For orientation, there’s magnetic North, gravity, or any conceivable cue that you might choose to face towards. How do cells orient themselves, however?
One of the primary ways in which cells orient themselves is by labeling regions of the cell membrane – by phosphorylating a type of lipid called phosphatidyl-inositol(4,5)bisphosphate [PI(4,5)P2] (green), so that it becomes [PI(3,4,5)P3] (purple), as shown by the image (Comer and Parent, 2007). As this reaction invovles the phosphorylation of the ‘3’ site of the inositol ring of carbon atoms, the enzyme which catalyzes this reaction is called PI-3 Kinase. (kinase = phosphorylating enzyme)
This reaction then provides the cue for a large number of PI(3,4,5)P3-binding proteins to move to a specific region within the cell, and creates subdomains for simulataneously coordinating different processes in different regions of the cell. The reverse enzymatic reaction is catalyzed by PTEN (Phosphatase and Tensin homolog deleted on chromosome 10), which was originally identified because its mutation (on chromosome 10) was correlated with a number of cancers.
The asymmetric distribution of PI-3 Kinase and PTEN establishes the cell polarity, but this polarity is reinforced by the activity of other proteins, such as cell surface receptors receiving orienting cues from outside the cell; Cdc42, Rac and Rho (the Rho family GTPases), which reorganize the cell’s skeleton (the cytoskeleton); and others (see figure from Wehrle-Haller and Imhof, 2003):
… but I’ve alluded to all of this before. The point being made here is that it’s really a very simple concept that cells have exploited to orient themselves – by figuring out how to label ‘this side up.’
- Comer FI, Parent CA. Phosphoinositides Specify Polarity during Epithelial Organ Development. Cell 2007 Jan 26;128(2):239-40. Pubmed
- Wehrle-Haller B, Imhof BA. Integrin-dependent pathologies. J Pathol. 2003 Jul;200(4):481-7. Pubmed