A Novel Interaction between Kinesin and p120 Modulates p120 Localization and Function

Abstract

p120-catenin exists in a membrane-associated cadherin-bound pool, a cytosolic pool that affects Rho GTPases, and a nuclear pool that is thought to associate with the methylation-relevant transcriptional repressor Kaiso. We show here that cytoplasmic p120 can also associate both directly and indirectly with the microtubule network, and that p120 traffics along microtubules toward their plus ends. The direct binding required most of the armadillo repeats and was mutually exclusive for interaction with E-cadherin. Perturbing the p120-microtubule interaction with nocodazole or taxol markedly affected both the tubulin interaction and the balance between cytoplasmic and nuclear p120. The indirect binding occurred via a novel interaction between a segment of the p120 N-terminal domain and conventional kinesin heavy chains. Selective uncoupling of the p120-kinesin interaction by overexpression of the respective p120 and kinesin-binding fragments promoted nuclear p120 accumulation. In addition, expression of full-length kinesin reduced the nuclear accumulation of p120 and blocked the branching phenotype associated with p120 overexpression. Taken together, the data suggest that kinesin affects both the targeting and activity of p120 at several cellular locations.

p120catenin alteration in cancer and its role in tumour invasion

“…First, p120catenin plays a role during cadherin biogenesis of certain types of cadherins by interacting with PTP1B and the cadherin precursor in the ER and favouring its translocation to the Golgi apparatus [63], although this mechanism does not seem to apply to E-cadherin [49]. Second, p120catenin interacts with conventional kinesins (figure 2), which promote p120catenin recruitment to the plasma membrane and prevent its accumulation in the nucleus [64]. Via its interaction with kinesins, p120catenin may support cadherin transport along microtubules to the site of adherens junction assembly [65].…”

“…In adherens junctions, p120catenin binds to the heavy chain of microtubule-associated motors kinesins [64,65] to facilitate cadherin trafficking. p120catenin interaction with kinesins suggests that p120catenin may control the distribution of its protein partners (e.g.…”

Emerging roles for p120-catenin in cell adhesion and cancer

“…The structural regions of p120 that influence nuclear localization have been described (van Hengel et al, 1999;Roczniak-Ferguson and Reynolds, 2003), and there is evidence that interactions between p120 and kinesin can strongly affect p120 nuclear trafficking (Yanagisawa et al, 2004). p120 interacts with Kaiso (Daniel and Reynolds, 1999), a member of the BTB/ POZ family of transcription factors, but the functional consequences are unknown.…”

“…Exact amino-acid locations of the known sites are listed. Their individual roles are unknown, but collectively, they participate in the dynamic regulation of p120 adhesive function p120-catenin, cell adhesion and motility AB Reynolds and A Roczniak-Ferguson (Chen et al, 2003;Yanagisawa et al, 2004). Kinesin may affect both the targeting and function of p120 at several cellular locations.…”

Noncentrosomal microtubules in C. elegans epithelia

“…The best-illustrated example is the targeting of E-cadherin to adherens junctions. Physical interactions between MTs, MT-based motors and adherens junction components have been reported in different cellular contexts (Chen et al, 2003;Ligon et al, 2001;Yanagisawa et al, 2004). MTs are likely to promote junction integrity and clustering of E-cadherin through both transport-dependent and -independent mechanisms.…”