Semester of Graduation
Spring 2026
Degree Type
Thesis
Degree Name
MASTER OF SCIENCE IN INTEGRATIVE BIOLOGY
Department
Department of Molecular and Cellular Biology
Committee Chair/First Advisor
Anton Bryantsev
Abstract
Akirin is a small protein involved in diverse processes, from mounting immune response to tissue development and nuclear trafficking. A mechanistic model that could explain such variety remains elusive. Recently, a highly conserved, four-amino acid C-terminal motif (SYLS) was described in Akirin. In human cells, this motif binds the 20S proteasome to promote its nuclear import in dividing cells.
Somatic adult muscles develop during the pupal stage and consist of highly differentiated muscle fibers specialized for specific functions (e.g., flight muscles power flight, while jump muscles initiate the escape response, etc..). In this study, we probed the involvement of Akirin in adult muscle development and differentiation, specifically the role of the SYLS motif.
Using molecular cloning, mutagenesis, in vivo knockdown (KD) and overexpression approaches, we demonstrate that muscle-specific KD of akirin is lethal in pupae and features thin, although properly differentiated, muscles. We further show that Akirin acts at early stages of myogenesis. When overexpressed in developing muscle tissue, the DSYLS mutant demonstrates thin muscles and partially recapitulates the KD phenotypes, which confirms significance of the SYLS motif for myogenesis. A yeast two-hybrid screen identified several, high-quality interaction partners for Akirin, and we genetically validated akirin interaction with kap-α3, a critical component of the nuclear import machinery.
Together, our data show that Akirin acts in myoblasts and that the conserved SYLS motif is essential, possibly by connecting this adaptor protein to targets that need to be imported from the cytoplasm into the nucleus.
Comments
Grants R15HL161738, R03 AG048496