Molecular modelling: a tool for understanding the cytoplasm-nucleus-nucleolus shuttling of the ceramide kinase-like protein

Ceramide kinase like (CERKL) is a protein implicated in the pathology of retinitis pigmentosa. In this study, the 3D predicted model of CERKL was determined by molecular modelling techniques. Our results predicted the presence in the CERKL protein of an N-terminal Pleckstrin Homology (PH) domain. Presence of a nuclear localization signal within the PH domain may suggest the role played by this domain in the CERKL cytoplasm--nucleus shuttling. We also predicted a putative nucleolar localization signal (NoLS) sequence within the Diacylglycerol Kinase (DAGK) C-terminal domain. We suggest that this NoLS sequence located in an exposed helix retains the CERKL protein in the nucleolus. Absence of the predicted NoLS sequence in the R257X and R379X variants may explain their location in the nucleus and their absence from nucleoli. These findings have important implications for our current understanding of the cytoplasm--nucleus--nucleolus CERKL protein shuttling.
Introduction Ceramide kinase like (CERKL) is a protein implicated in a form of autosomal recessive retinitis pigmentosa (RP), RP26 [1]. CERKL is a homolog of Ceramide kinase (CERK) sharing 50% [...]