Cilia are tiny hair-like microtubule-based cellular projections found on almost every cell-type of the vertebrate body. Motile cilia on epithelial cells ensure directional fluid flow is achieved so when disrupted this leads to severe ciliopathies like Primary Ciliary Dyskinesia (PCD). An intricate microtubule and protein arrangement within cilia, the axoneme, is decorated with macromolecular AAA+ motors along the inner and outer rows known as inner and outer dynein arms respectively which generate motility. PCD- causing mutations are common in axonemal dyneins as well the dynein axonemal assembly factors (DNAAFs) which build the motors. Of the 19 identified DNAAFs, ZMYND10 /DNAAF7 interacts with the Hsp90 co-chaperone, FKBP8 to potentially drive the maturation of catalytic dynein heavy chain subunits. What this putative chaperone complex structurally looks like and where specifically it functions in the cell are unknown. Using bioinformatics, a structural model for this putative complex is predicted and evaluated. Potential interactors of DNAAF7 are elucidated through analysis of endogenous immunoprecipitations and mass spectrometry datasets from primary human airway ciliated cells. The subcellular location of where this complex may be functioning is delineated through immunostaining assays which hint at the involvement of the endoplasmic reticulum and mitochondria in ciliary dynein assembly.
Investigating the Role of a Putative Chaperone Complex in Ciliary Dynein Assembly
Burnet, B. (Author). 3 Oct 2023
Student thesis: Master's Thesis › Master of Science by Research (MScR)