Palmitoylation-dependent CDKL5-PSD-95 interaction regulates synaptic targeting of CDKL5 and dendritic spine development.

The X-linked gene cyclin-dependent kinase-like 5 (CDKL5) is mutated in severe neurodevelopmental disorders, including some forms of atypical Rett syndrome, but the function and regulation of CDKL5 protein in neurons remain to be elucidated. Here, we show that CDKL5 binds to the scaffolding protein postsynaptic density (PSD)-95, and that this binding promotes the targeting of CDKL5 to excitatory synapses. Interestingly, this binding is not constitutive, but governed by palmitate cycling on PSD-95.

Secretome-derived isotope tags (SDIT) reveal adipocyte-derived apolipoprotein C-I as a predictive marker for cardiovascular disease.

We developed a quantitative strategy, named secretome-derived isotopic tag (SDIT), to concurrently identify and quantify the adipocyte-secreted plasma proteins from normal and high-fat-diet (HFD) induced obese mice, based on the application of isotope-labeled secreted proteins from cultured mouse adipocytes as internal standards. We detected 197 proteins with significant changes between normal and obese mice plasma. Importantly, a novel adipocyte-secreted plasma protein, apolipoprotein C-I (apoC-I), significantly increased in the obese mice plasma.

A comprehensive and non-prefractionation on the protein level approach for the human urinary proteome: touching phosphorylation in urine.

Increasing attention has been paid to the urinary proteome because it holds the promise of discovering various disease biomarkers. However, most of the urine proteomics studies routinely relied on protein pre-fractionation and so far did not present characterization on phosphorylation status. Two robust approaches, integrated multidimensional liquid chromatography (IMDL) and Yin-yang multidimensional liquid chromatography (MDLC) tandem mass spectrometry, were recently developed in our laboratory, with high-coverage identification of peptide mixtures.

Concurrent quantification of proteome and phosphoproteome to reveal system-wide association of protein phosphorylation and gene expression.

Reversible phosphorylation of proteins is an important process modulating cellular activities from upstream, which mainly involves sequential phosphorylation of signaling molecules, to downstream where phosphorylation of transcription factors regulates gene expression. In this study, we combined quantitative labeling with multidimensional liquid chromatography-mass spectrometry to monitor the proteome and phosphoproteome changes in the initial period of adipocyte differentiation. The phosphorylation level of a specific protein may be regulated by a kinase or phosphatase without involvement of gene expression or as a phenomenon that accompanies the alteration of its gene expression.

Temporal and spatial profiling of nuclei-associated proteins upon TNF-alpha/NF-kappaB signaling.

The tumor necrosis factor (TNF)-alpha/NF-kappaB-signaling pathway plays a pivotal role in various processes including apoptosis, cellular differentiation, host defense, inflammation, autoimmunity and organogenesis. The complexity of the TNF-alpha/NF-kappaB signaling is in part due to the dynamic protein behaviors of key players in this pathway. In this present work, a dynamic and global view of the signaling components in the nucleus at the early stages of TNF-alpha/NF-kappaB signaling was obtained in HEK293 cells, by a combination of subcellular fractionation and stable isotope labeling by amino acids in cell culture (SILAC).

Localized-statistical quantification of human serum proteome associated with type 2 diabetes.

Background: Recent advances in proteomics have shed light to discover serum proteins or peptides as biomarkers for tracking the progression of diabetes as well as understanding molecular mechanisms of the disease.

Results: In this work, human serum of non-diabetic and diabetic cohorts was analyzed by proteomic approach. To analyze total 1377 high-confident serum-proteins, we developed a computing strategy called localized statistics of protein abundance distribution (LSPAD) to calculate a significant bias of a particular protein-abundance between these two cohorts.