Should activin βC be more than a fading snapshot in the activin/TGFβ family album?

The activin growth factors consist of dimeric proteins made up of activin β subunits and have been shown to be essential regulators of diverse systems in physiology. Four subunits are known to be expressed in mammalian cells: βA, βB, βC, and βE. Surprisingly, deletion of activin βC and βE subunits in vivo does not affect embryonic development or adult physiology which has led to the activin βC and βE subunits being regarded as non-essential and unimportant. The steady accumulation of circumstantial evidence to the contrary has led this lab to reassess the role of the activin βC subunit. Activin βC protein is expressed more widely than indicated by mRNA localisation. Experiments overexpressing activin βC subunit or adding exogenous Activin C in vitro are contradictory but suggest roles for activin βC in regulating Activin A action in apoptosis and homeostasis. Sequestration of βA subunits by dimerisation with βC subunits to form Activin AC represents an intracellular regulator of Activin A bioactivity. Activins play a pivotal role in normal physiology and carcinogenesis, so any molecule, such as the activin βC subunit, that can affect activin action is potentially significant. Advancing our understanding of the physiological role of the activin βC subunit requires new tools and reagents. Direct detection of the Activin AC dimer will be essential and will necessitate the purification of heteromeric Activin AC protein. In addition, there is a need for the development of an in vivo model of activin βC subunit overexpression. With development of these tools, research into activin action in development and physiology can expand to include the less well understood members of the activin family such as activin βC.