Characterization of the putative GTPase activity of the Ellis van Creveld protein 1

Abstract

Ellis van Creveld (EvC) syndrome is a genetic disorder characterized by mild short stature, postaxial polydactyly, dysplastic nails and teeth. Loss‐of‐function EVC1 and EVC2 proteins resulting from mutations in EVC1 and EVC2 genes, respectively, have been identified as the primary causes of EvC syndrome. Essential to their function is the physical interaction of EVC1 and EVC2 proteins at the base of the primary cilium, where this complex regulates the Sonic and Indian hedgehog (Hh) signaling systems. Recent studies have revealed that this EVC1‐EVC2 protein complex is tethered to the base of the primary cilium by another complex comprising of two newly identified proteins, EFCAB7 and IQCE. Together, this multiprotein complex positively regulates downstream processes after signaling activation by hedgehog proteins. The presence of a putative P‐loop sequence in EVC1 strongly suggests that its interaction with EVC2 is dependent on nucleotide hydrolysis. Using protein fragments, we have experimental evidence that suggest that EVC1 possesses an intrinsic GTPase activity conferred by the presence of the P‐loop. This observation may provide insight into the function and regulation of the EVC1‐EVC2 complex in hedgehog signaling pathways.Support or Funding InformationWelch Foundation Grant # AN‐0008FRG‐RCA Grant, SFASUThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.