Distal motor latency and residuallatency as sensitive markersof anti-MAG polyneuropathy

Abstract.: There is debate whether the terminal latency index (TLI) is a sensitive marker for polyneuropathy with anti-myelinassociated-glycoprotein antibodies (anti-MAGP). We examined 6 patients with an anti-MAGP and 6 patients with a chronic inflammatory demyelinating polyneuropathy (CIDP). The electroneurographic features studied were: distal compound motor action potential (CMAP), distal motor latency (DML), motor conduction velocity (MCV) elbow to wrist (distal MCV), MCV axilla to elbow (proximal MCV), MCV distal/proximal, terminal latency index (TLI), residual latency (RL), F-wave, and modified F ratio.We found significant differences between anti-MAGP and CIDP for DML and for RL.No significant differences were found for TLI and the other measures. The TLI values were not significant probably because our patients had a longer duration of disease,which supports the hypothesis of a distal to proximal progression of conduction slowing over time. We propose that a residual latency >4.0 and a distal motor latency >7.0 are strongly suggestive for an anti- MAG

Phosphoproteomics Profiling Defines a Target Landscape of the Basophilic Protein Kinases AKT, S6K, and RSK in Skeletal Myotubes

Phosphorylation-dependent signal transduction plays an important role in regulating the functions and fate of skeletal muscle cells. Central players in the phospho-signaling network are the protein kinases AKT, S6K, and RSK as part of the PI3K-AKT-mTOR-S6K and RAF-MEK-ERK-RSK pathways. However, despite their functional importance, knowledge about their specific targets is incomplete because these kinases share the same basophilic substrate motif RxRxxp[ST]. To address this, we performed a multifaceted quantitative phosphoproteomics study of skeletal myotubes following kinase inhibition. Our data corroborate a cross talk between AKT and RAF, a negative feedback loop of RSK on ERK, and a putative connection between RSK and PI3K signaling. Altogether, we report a kinase target landscape containing 49 so far unknown target sites. AKT, S6K, and RSK phosphorylate numerous proteins involved in muscle development, integrity, and functions, and signaling converges on factors that are central for the skeletal muscle cytoskeleton. Whereas AKT controls insulin signaling and impinges on GTPase signaling, nuclear signaling is characteristic for RSK. Our data further support a role of RSK in glucose metabolism. Shared targets have functions in RNA maturation, stability, and translation, which suggests that these basophilic kinases establish an intricate signaling network to orchestrate and regulate processes involved in translation