WAVE facilitates polarized E-cadherin transport.

Abstract

Cadherin dynamics drive morphogenesis, while defects in cadherin polarity contribute to diseases, including cancers. However, the forces polarizing cadherin membrane distribution are not well understood. We previously showed that WAVE-dependent branched actin polarizes cadherin distribution and suggested that one mechanism is protein transport. While previous studies suggested that WAVE is enriched at various endocytic organelles, the role of WAVE in protein traffic is understudied. Here we test the model that WAVE regulates cadherin by polarizing its transport. In support of this model we show that 1) endogenously tagged WAVE accumulates in vivo at several endocytic organelles, including recycling endosomes and at the Golgi; 2) likewise, cadherin protein accumulates at recycling endosomes and the Golgi; 3) loss of WAVE components reduces cadherin accumulation at apically directed RAB-11-positive recycling endosomes and increases accumulation at the Golgi. In addition, live imaging illustrates that dynamics and velocity of recycling endosomes enriched for RAB-11::GFP and RFP::RME-1 are reduced in animals depleted of WAVE components and RAB-11::GFP movements are misdirected, suggesting that WAVE powers and directs their movements. This in vivo study demonstrates the importance of WAVE in promoting polarized transport in epithelia and supports a model that WAVE promotes cell-cell adhesion and polarity by promoting cadherin transport.