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25 Sep 2019

Polo-like kinase 4 maintains integrity of centriolar satellites

By nickwiecien

RA Denu et al recently published a paper on the importance of polo-like kinase 4 for centriolar satellite integrity in the Journal of Biological Chemistry.

Polo-like kinase 4 (PLK4), a Ser/Hr protein kinase, is the “master regulator” of centriole duplication and can also play a role in centrosome function. Centrioles are cell organelles which are responsible for cell division. In addition, centrioles are housed in other organelles, called centrosomes. 
This study was an attempt to identify additional proteins regulated by PLK4. To do this, scientists generated an RPE-1 human cell line and genetically engineered analog sensitive PLK4As.

Scientists found that Ser-78 is important for maintaining the integrity of centriolar satellites, as this is where PLK4 phosphorylates CEP131. Ser-78 in centrosomal protein 131 is a direct substrate of PLK4.

Another finding is that inhibiting PLK4 or using a nonphosphorylatable CEP131 tended to result in “dispersed” centriolar satellites.

18 Sep 2019

CZE and Mass Spectrometry Leads to Considerable Phosphopeptide Identification

By nickwiecien

Zhang et al demonstrated the importance and utility of Single-Shot Capillary Zone Electrophoresis in the Journal of Proteome Research.

Capillary zone electrophoresis (CZE) is a practical tool in exploring and interpreting post-translational modifications in proteins. To examine the usefulness of single-shot CZE with mass spectrometry through the analysis of phosphoproteomics, researchers used CZE separations with the Orbitrap Fusion Lumos Tribrid platform, and used a linear-polyacrylamide-coated capillary with low electroosmotic flow for separation.

Researchers found that larger injection volumes led to broader peaks and less phosphopeptide identifications. Additionally, in this single-shot phosphoproteome analysis, researchers found 4405 phosphopeptides out of an original 220 ng enriched phosphopeptides from a mouse brain.

Data for this study is available in the ProteomeXchange with identified PXD012888.

Graphical abstract for Zhang et al. This graph shows how Base Peak Intensity compares to Migration Time (in minutes). It appears that base peak intensity is higher during the 38 minute mark, the 63 minute mark, and the 65 minute mark.
11 Sep 2019

NCQBCS Scientists Publish on Essential Phosphatase Pptc7

By nickwiecien

Niemi et al analyzed a Pptc7 matrix phosphatase in mice in a recent issue of Nature Communications.

This paper addressed the functionality of phosphorylation in mitochondrial proteins. While mitochondrial proteins tend to have a lot of phosphorylation, it is also possible that protein dephosphorylation (the opposite process) may be significant in controlling various mitochondrial processes.

To test this, researchers deleted the matrix phosphatase Pptc7 from mice using the CRISPR-Cas9. As a result, mice were born with normal transcript levels but less mitochondria and protein in their tissues. They also had more phosphorylation in certain mitochondrial proteins. These mice developed hypoketonic hypoglycemia, had higher levels of acylcarnitines and serum lactate, and died shortly after being born. 

Analyzing this data, researchers pinpointed that the protein translocase complex subunit Timm50 is probably a Pptc7 substrate whose phosphorylation lowers import activity.  This data also demonstrates that Pptc7 is necessary for healthy mammalian mitochondrial processes, such as metabolism, and biogenesis after birth. 

04 Sep 2019

Brademan Paper on the Interactive Peptide Spectral Annotator

By nickwiecien

Brademan et al unveiled the Interactive Peptide Spectral Annotator (IPSA), in a recent issue of Molecular and Cellular Proteomics.

The IPSA is an interactive and easily-accessible web-based annotator that can be used to conceptualize and characterize peptides with mass spectra. This tool, which can visualize peptides collected from different experimental and instrumental sources, has a variety of purposes including creating figures for publication, annotating spectra for negative-mode ionization and the like.

The IPSA can be accessed through this link:
http://www.interactivepeptidespectralannotator.com

21 May 2019

McKetney Publishes “Proteomic Atlas of the Human Brain in Alzheimer’s Disease”

By nickwiecien

Justin McKetney et. al. recently published a paper on neurodegenerative diseases of the brain, such as Alzheimer’s disease (AD). Using state-of-the-art mass spectrometry, the group identified a core brain proteome where substantial differences were identified between previous proteomic studies of mature adult brains and their aged cohort. These findings suggest considerable value in examining specifically the brain proteome of aged human populations and can serve as a guide for how specific regions of the brain are affected by aging and neurodegeneration.

Graphical abstract for McKetney et al depicting areas of the brain studies, and methods used for creating a proteomic atlas: protein extraction, fractionation, chromatography, tandem MS, and Database search.
30 Mar 2018

Caloric Restriction Engages Hepatic RNA Processing Mechanisms in Rhesus Monkeys

By nickwiecien

Caloric restriction extends lifespan and delays aging in diverse species. On pp. 677–688 of the current issue of Cell Metabolism, Rhoads et al. integrated large-scale data from the hepatic transcriptome, proteome, and metabolome of rhesus monkeys after 2 years on a 30% calorie-restricted diet to reveal multi-modal mechanisms driven by calorie restriction to rewire metabolism. The panels of the cover image represent the four distinct regulatory strategies recruited by caloric restriction: transcriptional, post-transcriptional, translational, and post-translational, each of which gives a different “view” of the unified and integrated molecular response to caloric restriction.

Graphical abstract for Rhoads et al, depicting the Hepatic CR-responsibe molecular network
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