Dynamic microtubules regulate the local concentration of E-cadherin at cell-cell contacts

Abstract

In contrast to the well-established relationship between cadherins and the actin cytoskeleton, the potential link between cadherins and microtubules (MTs) has been less extensively investigated. We now identify a pool of MTs that extend radially into cell-cell contacts and are inhibited by manoeuvres that block the dynamic activity of MT plus-ends (e.g. in the presence of low concentrations of nocodazole and following expression of a CLIP-170 mutant). Blocking dynamic MTs perturbed the ability of cells to concentrate and accumulate E-cadherin at cell-cell contacts, as assessed both by quantitative immunofluorescence microscopy and fluorescence recovery after photobleaching (FRAP) analysis, but did not affect either transport of E-cadherin to the plasma membrane or the amount of E-cadherin expressed at the cell surface. This indicated that dynamic MTs allow cells to concentrate E-cadherin at cell-cell contacts by regulating the regional distribution of E-cadherin once it reaches the cell surface. Importantly, dynamic MTs were necessary for myosin II to accumulate and be activated at cadherin adhesive contacts, a mechanism that supports the focal accumulation of E-cadherin. We propose that this population of MTs represents a novel form of cadherin-MT cooperation, where cadherin adhesions recruit dynamic MTs that, in turn, support the local concentration of cadherin molecules by regulating myosin II activity at cell-cell contacts.

Solute carrier family 3 member 2 (Slc3a2) controls yolk syncytial layer (YSL) formation by regulating microtubule networks in the zebrafish embryo

“…How, then, can Slc3a2 modulate plasma membrane dynamics via microtubules? It is known that microtubule dynamics affect the regional distribution of adhesion molecules (38)(39)(40) and turnover of adherence junctions (41), thereby regulating adhesive strength and the integrity of cell-cell contacts. One possibility is that the local distribution of Slc3a2 regionally protects the microtubule networks, which in turn feed back on the localization of Slc3a2 or affect cellular distribution of other adhesion molecules (e.g., E-cadherin), thereby regulating the plasma membrane dynamics.…”

EMT, the cytoskeleton, and cancer cell invasion

“…One protein replacing α-catenin in the E-cadherin/β-catenin complex to SAJ could be eplin, a newly identified actin-binding protein [26]. The juxtamembrane domain of E-cadherin binds to p120-catenin which is important in surface tracking, lysosomal degradation and correct membrane localization of Ecadherin [27][28][29][30]. Furthermore, p120-catenin plays an elementary role in the stability of epithelial cell-cell adhesion by repressing the activity of RhoA and activating Rac and Cdc42 [31][32][33].…”

Adherens Junction: Molecular Architecture and Regulation

“…However, MTs have occasionally been observed to be located in a close proximity to the AJ, running parallel to this junction. Moreover, the radially extending MTs are targeted to the AJs with their plus ends in a CLIP-170-dependent manner, and blocking of the MT extension toward the AJs causes a reduction in the accumulation of junctional E-cadherin (Stehbens et al 2006). In addition, dynein was found to bind b-catenin, and this b-catenin-associated dynein was proposed to tether MTs to cell junctions (Ligon et al 2001;Shaw et al 2007).…”