PROJECT SUMMARY
Mammalian cells often use their actin cytoskeleton simultaneously for multiple functions, including cell motility,
endocytosis, vesicular trafficking, and to establish and maintain cell polarity. Although they accomplish different
tasks, functionally distinct actin networks share structural components and regulators that can include
polymerization factors, polymer bundlers, and proteins that promote network turnover. This molecular
multitasking by mammalian cells makes it difficult to determine how cells control subsets of actin functions. In
contrast, budding and fission yeast have highly simplified actin networks that have been used to develop
simple models of actin network control. The vast differences between yeast and human actin networks,
howevxer, make it difficult to understand which principles of actin cytoskeletal regulation are shared. Chytrid
fungi represent a natural bridge between the well-understood actin networks of yeast and the elaborate actin
networks of human cells for three reasons. First, the evolutionary position of chytrids falls between yeast and
human cells. Second, they have retained important actin regulators that have been lost by yeast, making their
actin networks are intermediate in complexity. Third, and most importantly, chytrid fungi undergo a natural
developmental transition from human-like crawling cells to a yeast-like cell type. We are therefore using chytrid
fungi to study the evolution and specification of actin networks relevant to human health. We have identified a
large number of chytrid actin cytoskeletal regulators similar to actin regulators found in human cells, as well as
additional fungal-specific actin regulators. We have also recently developed methods to control the switch from
the human-like to the yeast-like cells, as well as methods for molecular transformation and exogenous gene
expression. We will use these approaches to determine the mechanisms that control animal-like and yeast-like
actin networks in chytrids and the developmental transitions between them. This work will help us determine
how actin regulatory systems give rise to the observed diversity of actin networks across developmental
transitions and evolutionary time.