Microtubules regulate disassembly of epithelial apical junctions

Abstract

Background: Epithelial tight junction (TJ) and adherens junction (AJ) form the apical junctional complex (AJC) which regulates cell-cell adhesion, paracellular permeability and cell polarity. The AJC is anchored on cytoskeletal structures including actin microfilaments and microtubules. Such cytoskeletal interactions are thought to be important for the assembly and remodeling of apical junctions. In the present study, we investigated the role of microtubules in disassembly of the AJC in intestinal epithelial cells using a model of extracellular calcium depletion.

Classical and desmosomal cadherins at a glance

“…The cues that select cadherins for a specific internalization pathway are not well understood, although substantial progress has been made for classical cadherins. For example, E-cadherin and VE-cadherin are typically internalized through clathrindependent pathways (Ivanov et al, 2004;Izumi et al, 2004;Le et al, 1999;Xiao et al, 2005). The clathrin adaptor protein complex 2 (AP-2) has been shown to associate with the cytoplasmic domains of VE-cadherin and E-cadherin and appears crucial for endocytosis of classical cadherins (Chiasson et al, 2009;Sato et al, 2011).…”

Microtubules CLASP to Adherens Junctions in epidermal progenitor cells

“…MT depolymerization inhibited junction disassembly, suggesting that MTs are required for cadherin endocytosis in this cellular system. 28 In our work using confluent primary mouse keratinocytes (mKer) we observed that treatment with noc did not disassemble AJs. In fact, the surface levels of cadherins increased with time, suggesting that most likely cadherins were not internalized.…”

KIF17 regulates RhoA-dependent actin remodeling at epithelial cell–cell adhesions

“…Kinesin-mediated transport on microtubules is used to both deliver and retrieve cadherin and other adhesion components to and from the plasma membrane (Chen et al, 2003;Ivanov et al, 2006;Krylyshkina et al, 2002;Mary et al, 2002;Nekrasova et al, 2011;Portereiko et al, 2004;Yanagisawa et al, 2004). Dynamic microtubule plus-ends, where KIF17 localizes with EB1 and APC (Jaulin and Kreitzer, 2010), can interact with proteins at the cortex and deposit microtubule plus-end-associated proteins that regulate cytoskeletal and junctional organization, such as APC, leading to the concentration of E-cadherin at cell-cell contacts ( 2006).…”

“…Both focal adhesions and the AJC are sites of microtubule plus-ends targeting and where cytoskeletal dynamics may be regulated locally (Chausovsky et al, 2000;Efimov et al, 2008;Ezratty et al, 2005;Waterman-Storer et al, 2000). These cortical adhesions are also sites of active membrane recycling and kinesin-dependent delivery and retrieval of transmembrane and membrane-cytoskeleton linkers (Chen et al, 2003;Ivanov et al, 2006;Krylyshkina et al, 2002). The effects of KIF17 on RhoA activity, actin and microtubule arrays, and on stability of the AJC lend support to the idea that KIF17 plays an important role in coordinating formation of nascent cell-cell adhesions with remodeling of actin and microtubules to initiate morphological polarization of epithelial cells.…”

“…Known collectively as the apical junctional complex (AJC), adherens junctions couple adjacent cells physically whereas tight junctions set boundaries between apical and basolateral membranes and control paracellular permeability (Guillot and Lecuit, 2013). Components of the AJC are delivered to the membrane by transport along microtubules (Chen et al, 2003;Ivanov et al, 2006;Mary et al, 2002;Nekrasova et al, 2011;Portereiko et al, 2004;Yanagisawa et al, 2004) and are anchored at adhesive sites by their association with actin and microtubule adaptors. As cell-cell adhesions mature, signaling molecules that also associate with the AJC induce changes in actin and microtubule arrays by modifying polymer dynamics and stability (Brieher and Yap, 2013;Chausovsky et al, 2000;Mege et al, 2006;Ratheesh et al, 2012).…”