Abstract
Mask family proteins were discovered in Drosophila to promote the activity of the transcriptional coactivator Yorkie (Yki), the sole fly homolog of mammalian YAP (YAP1) and TAZ (WWTR1). The molecular function of Mask, or its mammalian homologs Mask1 (ANKHD1) and Mask2 (ANKRD17), remains unclear. Mask family proteins contain two ankyrin repeat domains that bind Yki/YAP as well as a conserved nuclear localisation sequence (NLS) and nuclear export sequence (NES), suggesting a role in nucleo-cytoplasmic transport. Here we show that Mask acts to promote nuclear import of Yki, and that addition of an ectopic NLS to Yki is sufficient to bypass the requirement for Mask in Yki-driven tissue growth. Mammalian Mask1/2 proteins also promote nuclear import of YAP, as well as stabilising YAP and driving formation of liquid droplets. Mask1/2 and YAP normally colocalise in a granular fashion in both nucleus and cytoplasm, and are co-regulated during mechanotransduction.
Highlights
The YAP/TAZ family of oncoproteins has a single homolog in Drosophila named Yorkie (Yki) that was discovered to control tissue growth in proliferating epithelia (Huang et al, 2005)
We began by examining whether Mask family proteins have a role in regulating the subcellular localisation of Yki, as we were unable to identify a direct transcriptional activation function for Mask in a GAL4 reporter assay (Figure 1—figure supplement 1)
We ruled out a possible role for Mask in promoting Yki nuclear import based on antibody staining for Yki in mask10.22 null mutant clones in the Drosophila wing disc, where Yki is mostly cytoplasmic (Sidor et al, 2013)
Summary
The YAP/TAZ family of oncoproteins has a single homolog in Drosophila named Yorkie (Yki) that was discovered to control tissue growth in proliferating epithelia (Huang et al, 2005). In response to mechanical stretching/flattening of cells, both Yki (Fletcher et al, 2018) and YAP/TAZ (Dupont et al, 2011; Wada et al, 2011; Zhao et al, 2007) can translocate from the cytoplasm to the nucleus. Both Yki (Manning et al, 2018) and YAP (Ege et al, 2018) undergo dynamic and continuous nuclear-cytoplasmic shuttling which must involve specific nuclear import and export factors. No nuclear import factors for the Yki/YAP/TAZ
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