Autism-related mutations inhibit export of key protein from endoplasmicreticulum uoftsukuba SciReports
In summary, here we found that the EF-hand motif in Hevin plays an important role for proper trafficking to the extracellular spaces. A loss of this domain causes protein accumulation in the ER and activates the UPR pathway. Furthermore, we found that ASD-associated mutation in which Trpis replaced with Arg exhibits a similar phenotype in cells. Importantly, in the hW647R mutant Hevin the hydrophobic core of the EF hand is exposed to the surface likely causing structural instability.
The primers used were as follows:Full-length Hevin reverse, 5′-ggagatcttcaaaagaggaggttttcatctatatcctcctc-3′;Hevin ΔEF inverse antisense, 5′-gtgttccatgggcaccaggg-3′;N-terminal Hevin reverse, 5′-gatggtctccagccaagagtctcttctcatcc-3′;C-terminal Hevin-Ndufa11 mutants reverse, 5′-tctgcagaattcaggacaccttgggggtag-3′;Hevin W633R mutant reverse, 5′-gcagtggccccgttccttc-3′;Hevin for SLiCE reverse, 5′-tataggggatgccacagcggttcccaag-3′;GST for SLiCE reverse, 5′-ttgtcgggatgtcacgatgcgg-3′;-deficient brains were...
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