S3, E and F). Overall, these data provide compelling evidence that p120 is required to localize PF-CBP1 CLASP2 to AJs in a normal physiological context. MT targeting to AJs with potential functional implications in the maintenance of proper cellcell adhesion in epidermal stem cells. == Introduction == Throughout the eukaryotic kingdom, the microtubule (MT) cytoskeleton functions in a wide range of fundamental physiological processes, including organelle positioning, mitosis, cell polarity, and migration (Olmsted and Borisy, 1973). In all these contexts, it is crucial that this dynamic cytoskeleton is usually precisely organized to preserve cellular functions. MTs are polarized polymers with a minus end anchored to an MT-organizing center, being PF-CBP1 usually the centrosome (Lders and Stearns, 2007). MTs radially grow from the MT-organizing center projecting their plus ends toward the cell membrane and recurrently undergo stochastic switches of growth and shrinkage, a process termed dynamic instability (Desai and Mitchison, 1997;Howard and Hyman, 2009). Capture of MT plus ends at cortical sites leads to a decrease in MT dynamic instability (Gundersen, 2002). Epithelial cells also develop noncentrosomal MTs that generally orient their minus ends toward the apical domain name, and their plus ends extend laterally toward the basal domain name (Bacallao et al., 1989;Bartolini and Gundersen, 2006). Previous findings have illustrated a dynamic cross talk between cadherins and MTs (Chausovsky et al., 2000;Waterman-Storer et al., 2000). Cadherin-mediated adhesion through adherens junctions (AJs) stabilizes MTs (Waterman-Storer et al., 2000) and is sufficient for their recruitment (Stehbens et al., 2006). Moreover, subsets of both MT plus ends (Ligon et al., 2001;Stehbens et al., 2006) and minus ends (Meng et al., 2008;Bellett et al., 2009) have been observed at AJs. Conversely, MT depolymerization has a negative effect on cadherin stability (Yap et al., 1995) and formation (Mary et al., 2002) but also on AJ disassembly (Ivanov et al., 2006), depending on the cell context. MT plus endtracking proteins (+TIPs;Akhmanova and Steinmetz, 2008) have been associated to AJs (Akhmanova et al., 2009). For example, dynein binds to the AJ protein -catenin (Ligon et al., 2001), and CLIP-170 localizes near cadherin clusters (Stehbens et al., 2006). That said, the molecular players underlying the MTAJ connection and their physiological significance in tissue homeostasis are still unfolding. Best known for its role as a regulator of cadherin stability at the cell membrane (Davis et al., 2003;Ishiyama et al., 2010), the AJ protein p120 is usually a strong candidate for regulating MTAJ dynamics. p120 has been reported to associate with MTs in a cadherin-independent manner (Franz and Ridley, 2004;Yanagisawa et al., 2004;Ichii and Takeichi, 2007). However, when bound to cadherins, p120 has been found to associate with the protein PLEKHA7, which in turn recruits the MT minus endbinding protein Nezha, leading to anchorage of MTs at mature AJs (Meng et al., 2008). One of the current challenges in the field is usually to determine which molecular interactions take place between MTs and AJs in primary cells and tissues and how they preserve cellular PF-CBP1 functions within a physiological context. During terminal differentiation in the stratified epidermis, MTs in suprabasal cells reorganize in a desmosome-dependent manner into cortical noncentrosomal arrays (Lechler and Fuchs, 2007;Simpson et al., 2011;Sumigray et al., 2011,2012). In contrast, mitotically active basal progenitors, which adhere through integrins to an underlying basement membrane of extracellular matrix proteins, display a paucity of desmosomes, and their lateral intercellular junctions are largely composed of AJs. Whether and/or how MTs are targeted to AJs in these basal stem cells is usually unknown. Here, we IL-23A report that PF-CBP1 this +TIP protein CLASP2 (CLIP-associated protein 2) localizes to AJs via p120 in primary basal mouse keratinocytes (mKer), and this interaction changes upon commitment to terminal differentiation. Our findings provide a new mechanism of MT targeting to AJs, with potential functional implications in the maintenance of proper cellcell adhesion in epidermal stem cells. == Results == == CLASP2 and p120 interact at AJs in primary mKer == The conversation between p120 and CLASP2 was initially identified in a yeast two-hybrid assay, screening a mouse skin cDNA expression library with the p120 N-terminal domain name as bait (1467 aa), in which 6% of the clones identified corresponded to CLASP2 (unpublished data). CLASP2 was first described as a CLIP-170 and CLIP-115 binding partner (Akhmanova et al., 2001), which stabilizes MT plus ends at the cell cortex (Mimori-Kiyosue et al., 2005;Drabek et al., 2006). As such, this made it.