Instead, a substitution of at least two nucleotides would be needed to generate the arginine-to-alanine mutation studied by Telezhkin43; thus, the R325A mutation is less likely to occur in vivo.
Now, in this issue of EMBO Molecular Medicine, Schumacher et al (2015) report that the same CUL3Δ403 459 mutation studied by McCormick et al (2014) is severely compromised in its ability to ubiquitinate WNKs, possibly due to altered structural flexibility.
The shape of the macroscopic I– V relationship was nearly linear for Cys-less CFTR and was not significantly altered by any of the mutations studied, nor did modification by either MTSES or MTSET have any significant effect on the shape of the I– V relationship.
The mutations studied here rather act by inducing functional changes of the acto-myosin interactions and, therefore, of the whole sarcomere [ 15, 17, 36].
These defects have been implicated by mutations studied in zebrafish models of SMA (Akten et al., 2011; Lotti et al., 2012; Sleeman, 2013), in other models of SMA (Sleeman, 2013) and in various models of mutations in ALS (Ling et al., 2013; Sleeman, 2013).
Yet, in stark contrast to the prominent pathologies caused by the mutations studied here, a complete loss of TRPV4 activity has only minor and late-onset effects on bone development.
In particular, we observed that ARCH driven by the mutations studied here doubled in frequency in successive decades after the age of 50, rising from 1.5% in those aged 50 59 to 19.5% in those aged 90 98.
We therefore decided to pool all the data on expansion and deletion sizes across all the mutants investigated to obtain sufficiently large datasets to clearly visualize distributions, on the explicit assumption that expansion and deletion sizes were not affected by the mutations studied.
Effects on cell proliferation by the detected mutations were studied by expressing wild-type and mutant Bcl11b in the cytokine-dependent hematopoietic progenitor cell line FDC-P1, lacking endogenous Bcl11b expression.
