SHULIN PACKAGES AXONEMAL OUTER DYNEIN ARMS FOR CILIARY TARGETING
The major finding of this study was the discovery of a new protein that inhibits ciliary dynein motors. The study also solves one of the first cryo-EM structures of any ciliary motor in the inhibited state - the newly discovered protein clusters the three catalytic subunits packaging the motor complex to prevent activation. I named the protein Shulin (Sanskrit: the one who wields the trident; aka DNAAF9).
Mali et al., Elife. 2018 Jun.
ZMYND10 FUNCTIONS IN A CHAPERONE RELAY DURING AXONEMAL DYNEIN ASSEMBLY.
This paper represents a paradigm shift in understanding the cellular pathophysiology of the motile cilia disease - Primary Ciliary Dyskinesia (PCD). Specifically, it sheds light on a chaperone-relay pathway involving ZMYND10 (aka DNAAF7) that contributes to dynein assembly. This study advances our understanding of PCD as a disease of protein mis-folding and opens up new paths to treatment by modulating the cells natural quality control systems.
Diggle, Moore, Mali et al., PloS Genet. 2014 Sep.
HEATR2 PLAYS A CONSERVED ROLE IN ASSEMBLY OF THE CILIARY MOTILE APPARATUS.
This paper is a multi-system functional characterisation of a key dynein assembly factor – HEATR2 (aka DNAAF5). It combines functional studies using Drosophila and mouse models with clinical investigations on PCD patients harbouring HEATR2 mutations. It identified HEATR2 as a key protein in dynein assembly that engages molecular heat-shock protein chaperones for dynein subunit folding/assembly.