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. Both actin and microtubules are polar, dynamic filaments formed of protein subunits. These subunits associate together and align in the same direction to form a polymer which has two distinct ends. These actin filament polymers and microtubule polymers are therefore intrinsically polar, and cytoskeleton-associated proteins can use this asymmetry for further biological functions. Motor proteins such as myosins, kinesins, and dynein catalyze unidirectional movement along actin or microtubules to transport cargo throughout the cell, and this process can also generate polarity through organization of cellular components . For instance, dynein has been associated with the transport of both Par3 and the Crumbs polarity protein to the apical region of the cell .
One of the first signals that initiates polarized actin cytoskeletal remodeling arises from the binding of extracellular matrix components to the integrin receptors on the basal plasma membrane. Integrin signaling activates Rac1 , which is involved in the organization of laminin within the basement membrane . In addition, activated Rac1 binds to the adaptor protein IRSp53 and causes the local activation of actin polymerization factors, which are then responsible for assembling a basal actin cortex . At the apical surface, signaling via adherens junctions recruits c-Src, which results in a similar activation of actin polymerization modules through Rac and Cdc42 GTPases . Several studies have also demonstrated the involvement of integrin-based adhesions and adherens junctions in the recruitment and polarized orientation of microtubules. In this regard, integrin-linked kinase (ILK) activated by integrin-beta1 signaling activates microtubule plus ends via adaptor proteins such as APC . The minus ends of microtubules in fully polarized epithelia cluster at the adherens junctions, where they are stabilized by proteins like ninein . Another recently-characterized protein CAMSAP3 (also known as Nezha) was found to tether the microtubule minus ends to the apical cortex .
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 . 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 .
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
- Li R, and Gundersen GG. Beyond polymer polarity: how the cytoskeleton builds a polarized cell. Nat. Rev. Mol. Cell Biol. 2008; 9(11):860-73. [PMID: 18946475]
- Li Z, Wang L, Hays TS, and Cai Y. Dynein-mediated apical localization of crumbs transcripts is required for Crumbs activity in epithelial polarity. J. Cell Biol. 2008; 180(1):31-8. [PMID: 18195099]
- Harris TJC, and Peifer M. The positioning and segregation of apical cues during epithelial polarity establishment in Drosophila. J. Cell Biol. 2005; 170(5):813-23. [PMID: 16129788]
- Berrier AL, Martinez R, Bokoch GM, and LaFlamme SE. The integrin beta tail is required and sufficient to regulate adhesion signaling to Rac1. J. Cell. Sci. 2002; 115(Pt 22):4285-91. [PMID: 12376560]
- O'Brien LE, Jou TS, Pollack AL, Zhang Q, Hansen SH, Yurchenco P, and Mostov KE. Rac1 orientates epithelial apical polarity through effects on basolateral laminin assembly. Nat. Cell Biol. 2001; 3(9):831-8. [PMID: 11533663]
- Yu W, Datta A, Leroy P, O'Brien LE, Mak G, Jou T, Matlin KS, Mostov KE, and Zegers MMP. Beta1-integrin orients epithelial polarity via Rac1 and laminin. Mol. Biol. Cell 2004; 16(2):433-45. [PMID: 15574881]
- Lee JL, and Streuli CH. Integrins and epithelial cell polarity. J. Cell. Sci. 2014; 127(Pt 15):3217-25. [PMID: 24994933]
- Sato T, Fujita N, Yamada A, Ooshio T, Okamoto R, Irie K, and Takai Y. Regulation of the assembly and adhesion activity of E-cadherin by nectin and afadin for the formation of adherens junctions in Madin-Darby canine kidney cells. J. Biol. Chem. 2005; 281(8):5288-99. [PMID: 16361708]
- Akhmanova A, and Steinmetz MO. Tracking the ends: a dynamic protein network controls the fate of microtubule tips. Nat. Rev. Mol. Cell Biol. 2008; 9(4):309-22. [PMID: 18322465]
- Mogensen MM, Malik A, Piel M, Bouckson-Castaing V, and Bornens M. Microtubule minus-end anchorage at centrosomal and non-centrosomal sites: the role of ninein. J. Cell. Sci. 2000; 113 ( Pt 17):3013-23. [PMID: 10934040]
- Moss DK, Bellett G, Carter JM, Liovic M, Keynton J, Prescott AR, Lane EB, and Mogensen MM. Ninein is released from the centrosome and moves bi-directionally along microtubules. J. Cell. Sci. 2007; 120(Pt 17):3064-74. [PMID: 17698918]
- Meng W, Mushika Y, Ichii T, and Takeichi M. Anchorage of microtubule minus ends to adherens junctions regulates epithelial cell-cell contacts. Cell 2008; 135(5):948-59. [PMID: 19041755]
- Toya M, Kobayashi S, Kawasaki M, Shioi G, Kaneko M, Ishiuchi T, Misaki K, Meng W, and Takeichi M. CAMSAP3 orients the apical-to-basal polarity of microtubule arrays in epithelial cells. Proc. Natl. Acad. Sci. U.S.A. 2015; 113(2):332-7. [PMID: 26715742]
- Mellman I, and Nelson WJ. Coordinated protein sorting, targeting and distribution in polarized cells. Nat. Rev. Mol. Cell Biol. 2008; 9(11):833-45. [PMID: 18946473]
- 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 J, Uhlén P, and Holmgren L. AmotL2 disrupts apical-basal cell polarity and promotes tumour invasion. Nat Commun 2014; 5:4557. [PMID: 25080976]