LaeA Control of Velvet Family Regulatory Proteins for Light-Dependent Development and Fungal Cell-Type Specificity

Abstract

VeA is the founding member of the velvet superfamily of fungal regulatory proteins. This protein is involved in light response and coordinates sexual reproduction and secondary metabolism in Aspergillus nidulans. In the dark, VeA bridges VelB and LaeA to form the VelB-VeA-LaeA (velvet) complex. The VeA-like protein VelB is another developmental regulator, and LaeA has been known as global regulator of secondary metabolism. In this study, we show that VelB forms a second light-regulated developmental complex together with VosA, another member of the velvet family, which represses asexual development. LaeA plays a key role, not only in secondary metabolism, but also in directing formation of the VelB-VosA and VelB-VeA-LaeA complexes. LaeA controls VeA modification and protein levels and possesses additional developmental functions. The laeA null mutant results in constitutive sexual differentiation, indicating that LaeA plays a pivotal role in inhibiting sexual development in response to light. Moreover, the absence of LaeA results in the formation of significantly smaller fruiting bodies. This is due to the lack of a specific globose cell type (Hülle cells), which nurse the young fruiting body during development. This suggests that LaeA controls Hülle cells. In summary, LaeA plays a dynamic role in fungal morphological and chemical development, and it controls expression, interactions, and modification of the velvet regulators. Numerous fungi have the potential to infect immunocompromised patients or to contaminate and spoil our nutrients. They represent an increasing danger that threatens public health and agriculture. This requires improved understanding of fungal growth, development, dissemination of spores, and mycotoxin production. We have discovered two related fungal specific protein complexes that provide a molecular link among spore formation, fungal development, and secondary metabolite production. The subunit allocation of both complexes depends on each other, and they share a common subunit. These complexes comprise three related and in fungi conserved proteins of the velvet family that function in concert with a known regulator of secondary metabolism, LaeA. This protein controls the formation of both complexes but is only a part of the trimeric complex. We found that this regulator of secondary metabolism also possesses several developmental control functions in gene expression. These protein complexes discovered in the fungal model system Aspergillus nidulans are conserved in fungal pathogens where they might provide novel insights for understanding growth, development, and interaction with their respective hosts.