Functional Modules

    Establishment of Cell Polarity[Edit]

    This is a stub page. Please help us describe more about the establishment of cell polarity by editing this page.

    Cell polarity refers to the intrinsic asymmetry observed in cells, either in their shape, structure, or organization of cellular components. Establishing and maintaining this polarity is often essential for correct cell function. A good example of a how cell polarity affects function can be seen in neurons, which are specialized for the transmission of electrical signals. A typical unipolar neuron has a highly distinctive shape and structure, with one end adapted to receive signals through highly branched dendrites. This signal is then transmitted down an axon, which can stretch the length of the body. At the other end of the cell is the axon terminal, where the synapses are located. These synapses can release chemical neurotransmitters in order to propagate the signal or effect an action such as muscle contraction.

    Most epithelial cells, migrating cells and developing cells require some form of cell polarity for their function. This polarity arises from interactions between chemical gradients, the organization of cellular components and cytoskeletal remodeling.

    Epithelial cells establish an apical-basal polarity, which results from cell membrane composition. The membrane facing the lumen or free surface is known as the apical membrane, and the membrane oriented away from the lumen, contacting the extracellular matrix, is known as the basolateral membrane. Epithelial cell polarity is achieved through localization of different protein complexes and phospholipids. The apical membrane is rich in PIP2, along with PAR and Crumbs complexes while the basal membrane contains PIP3, and the Scribble protein complex [1, 2, 3].

    As well as the asymmetric organization of cellular components, polarity can also be defined through the structural orientation of the cytoskeleton, in particular, actin filaments and microtubules. This is important in cell migration and motility, which requires a front-rear polarity in order to determine the direction of movement.

    When a cell is unable to polarize correctly, the resulting loss or mutation of function can lead to disease. Some cell polarity defects include cystic fibrosis, cardiac arrhythmia and oncogenesis [4]. One protein which has been implicated in tumour invasion is AmotL2, a membrane associated scaffold protein that regulates expansion of the aortic lumen. Stress related activation of AmotL2 disrupts apical/basal polarity by preventing PAR and Crumb complexes from reaching the apical membrane, leading to tumour formation and invasion [5]. Members of the Amot protein family have recently been implicated in regulation of the Hippo signaling pathway by sequestering the Hippo effector Yap1 [6]. 

    References

    1. St Johnston D., Ahringer J. Cell polarity in eggs and epithelia: parallels and diversity. Cell 2010; 141(5). [PMID: 20510924]
    2. Gassama-Diagne A., Yu W., ter Beest M., Martin-Belmonte F., Kierbel A., Engel J., Mostov K. Phosphatidylinositol-3,4,5-trisphosphate regulates the formation of the basolateral plasma membrane in epithelial cells. Nat. Cell Biol. 2006; 8(9). [PMID: 16921364]
    3. Martin-Belmonte F., Gassama A., Datta A., Yu W., Rescher U., Gerke V., Mostov K. PTEN-mediated apical segregation of phosphoinositides controls epithelial morphogenesis through Cdc42. Cell 2007; 128(2). [PMID: 17254974]
    4. Mellman I., Nelson WJ. Coordinated protein sorting, targeting and distribution in polarized cells. Nat. Rev. Mol. Cell Biol. 2008; 9(11). [PMID: 18946473]
    5. Mojallal M., Zheng Y., Hultin S., Audebert S., van Harn T., Johnsson P., Lenander C., Fritz N., Mieth C., Corcoran M., Lembo F., Hallström M., Hartman J., Mazure NM., Weide T., Grandér D., Borg JP., Uhlén P., Holmgren L. AmotL2 disrupts apical-basal cell polarity and promotes tumour invasion. Nat Commun 2014; 5. [PMID: 25080976]
    6. Moleirinho S., Guerrant W., Kissil JL. The Angiomotins–from discovery to function. FEBS Lett. 2014; 588(16). [PMID: 24548561]
    Updated on: Thu, 22 Jan 2015 05:56:06 GMT
    History