Hyperexcitability and reduced low threshold potassium currents in auditory neurons of mice lacking the channel subunit Kv1.1

A low voltage-activated potassium current, IKL, is found in auditory neuron types that have low excitability and precisely preserve the temporal pattern of activity present in their presynaptic inputs. The gene Kcnal codes for Kv1.1 potassium channel subunits, which combine in expression systems to produce channel tetramers with properties similar to those of IKL, including sensitivity to dendrotoxin (DTX). Kv1.1 is strongly expressed in neurons with IKL, including auditory neurons of the medial nucleus of the trapezoid body (MNTB). We therefore decided to investigate how the absence of Kv1.1 affected channel properties and function in MNTB neurons from mice lacking Kcnal. We used the whole cell version of the patch clamp technique to record from MNTB neurons in brainstem slices from Kcnal-null (−/−) mice and their wild-type (+/+) and heterozygous (+/−) littermates. There was an IKL in voltage-clamped −/− MNTB neurons, but it was about half the amplitude of the IKL in +/+ neurons, with otherwise similar properties. Consistent with this, −/− MNTB neurons were more excitable than their +/+ counterparts; they fired more than twice as many action potentials (APs) during current steps, and the threshold current amplitude required to generate an AP was roughly halved. +/− MNTB neurons had excitability and IKL amplitudes identical to the +/+ neurons. The IKL remaining in −/− neurons was blocked by DTX, suggesting the underlying channels contained subunits Kv1.2 and/or Kv1.6 (also DTX-sensitive). DTX increased excitability further in the already hyperexcitable −/− MNTB neurons, suggesting that −/−IKL limited excitability despite its reduced amplitude in the absence of Kv1.1 subunits

The State of the Human Proteome in 2012 as Viewed through PeptideAtlas

The Human Proteome Project was launched in September 2010 with the goal of characterizing at least one protein product from each protein-coding gene. Here we assess how much of the proteome has been detected to date via tandem mass spectrometry by analyzing PeptideAtlas, a compendium of human derived LC–MS/MS proteomics data from many laboratories around the world. All data sets are processed with a consistent set of parameters using the Trans-Proteomic Pipeline and subjected to a 1% protein FDR filter before inclusion in PeptideAtlas. Therefore, PeptideAtlas contains only high confidence protein identifications. To increase proteome coverage, we explored new comprehensive public data sources for data likely to add new proteins to the Human PeptideAtlas. We then folded these data into a Human PeptideAtlas 2012 build and mapped it to Swiss-Prot, a protein sequence database curated to contain one entry per human protein coding gene. We find that this latest PeptideAtlas build includes at least one peptide for each of ∼12500 Swiss-Prot entries, leaving ∼7500 gene products yet to be confidently cataloged. We characterize these “PA-unseen” proteins in terms of tissue localization, transcript abundance, and Gene Ontology enrichment, and propose reasons for their absence from PeptideAtlas and strategies for detecting them in the future

The State of the Human Proteome in 2012 as Viewed through PeptideAtlas

The Human Proteome Project was launched in September 2010 with the goal of characterizing at least one protein product from each protein-coding gene. Here we assess how much of the proteome has been detected to date via tandem mass spectrometry by analyzing PeptideAtlas, a compendium of human derived LC–MS/MS proteomics data from many laboratories around the world. All data sets are processed with a consistent set of parameters using the Trans-Proteomic Pipeline and subjected to a 1% protein FDR filter before inclusion in PeptideAtlas. Therefore, PeptideAtlas contains only high confidence protein identifications. To increase proteome coverage, we explored new comprehensive public data sources for data likely to add new proteins to the Human PeptideAtlas. We then folded these data into a Human PeptideAtlas 2012 build and mapped it to Swiss-Prot, a protein sequence database curated to contain one entry per human protein coding gene. We find that this latest PeptideAtlas build includes at least one peptide for each of ∼12500 Swiss-Prot entries, leaving ∼7500 gene products yet to be confidently cataloged. We characterize these “PA-unseen” proteins in terms of tissue localization, transcript abundance, and Gene Ontology enrichment, and propose reasons for their absence from PeptideAtlas and strategies for detecting them in the future

The State of the Human Proteome in 2012 as Viewed through PeptideAtlas

The Human Proteome Project was launched in September 2010 with the goal of characterizing at least one protein product from each protein-coding gene. Here we assess how much of the proteome has been detected to date via tandem mass spectrometry by analyzing PeptideAtlas, a compendium of human derived LC–MS/MS proteomics data from many laboratories around the world. All data sets are processed with a consistent set of parameters using the Trans-Proteomic Pipeline and subjected to a 1% protein FDR filter before inclusion in PeptideAtlas. Therefore, PeptideAtlas contains only high confidence protein identifications. To increase proteome coverage, we explored new comprehensive public data sources for data likely to add new proteins to the Human PeptideAtlas. We then folded these data into a Human PeptideAtlas 2012 build and mapped it to Swiss-Prot, a protein sequence database curated to contain one entry per human protein coding gene. We find that this latest PeptideAtlas build includes at least one peptide for each of ∼12500 Swiss-Prot entries, leaving ∼7500 gene products yet to be confidently cataloged. We characterize these “PA-unseen” proteins in terms of tissue localization, transcript abundance, and Gene Ontology enrichment, and propose reasons for their absence from PeptideAtlas and strategies for detecting them in the future

The State of the Human Proteome in 2012 as Viewed through PeptideAtlas

The Human Proteome Project was launched in September 2010 with the goal of characterizing at least one protein product from each protein-coding gene. Here we assess how much of the proteome has been detected to date via tandem mass spectrometry by analyzing PeptideAtlas, a compendium of human derived LC–MS/MS proteomics data from many laboratories around the world. All data sets are processed with a consistent set of parameters using the Trans-Proteomic Pipeline and subjected to a 1% protein FDR filter before inclusion in PeptideAtlas. Therefore, PeptideAtlas contains only high confidence protein identifications. To increase proteome coverage, we explored new comprehensive public data sources for data likely to add new proteins to the Human PeptideAtlas. We then folded these data into a Human PeptideAtlas 2012 build and mapped it to Swiss-Prot, a protein sequence database curated to contain one entry per human protein coding gene. We find that this latest PeptideAtlas build includes at least one peptide for each of ∼12500 Swiss-Prot entries, leaving ∼7500 gene products yet to be confidently cataloged. We characterize these “PA-unseen” proteins in terms of tissue localization, transcript abundance, and Gene Ontology enrichment, and propose reasons for their absence from PeptideAtlas and strategies for detecting them in the future

The State of the Human Proteome in 2012 as Viewed through PeptideAtlas

The Human Proteome Project was launched in September 2010 with the goal of characterizing at least one protein product from each protein-coding gene. Here we assess how much of the proteome has been detected to date via tandem mass spectrometry by analyzing PeptideAtlas, a compendium of human derived LC–MS/MS proteomics data from many laboratories around the world. All data sets are processed with a consistent set of parameters using the Trans-Proteomic Pipeline and subjected to a 1% protein FDR filter before inclusion in PeptideAtlas. Therefore, PeptideAtlas contains only high confidence protein identifications. To increase proteome coverage, we explored new comprehensive public data sources for data likely to add new proteins to the Human PeptideAtlas. We then folded these data into a Human PeptideAtlas 2012 build and mapped it to Swiss-Prot, a protein sequence database curated to contain one entry per human protein coding gene. We find that this latest PeptideAtlas build includes at least one peptide for each of ∼12500 Swiss-Prot entries, leaving ∼7500 gene products yet to be confidently cataloged. We characterize these “PA-unseen” proteins in terms of tissue localization, transcript abundance, and Gene Ontology enrichment, and propose reasons for their absence from PeptideAtlas and strategies for detecting them in the future

The State of the Human Proteome in 2012 as Viewed through PeptideAtlas

The Human Proteome Project was launched in September 2010 with the goal of characterizing at least one protein product from each protein-coding gene. Here we assess how much of the proteome has been detected to date via tandem mass spectrometry by analyzing PeptideAtlas, a compendium of human derived LC–MS/MS proteomics data from many laboratories around the world. All data sets are processed with a consistent set of parameters using the Trans-Proteomic Pipeline and subjected to a 1% protein FDR filter before inclusion in PeptideAtlas. Therefore, PeptideAtlas contains only high confidence protein identifications. To increase proteome coverage, we explored new comprehensive public data sources for data likely to add new proteins to the Human PeptideAtlas. We then folded these data into a Human PeptideAtlas 2012 build and mapped it to Swiss-Prot, a protein sequence database curated to contain one entry per human protein coding gene. We find that this latest PeptideAtlas build includes at least one peptide for each of ∼12500 Swiss-Prot entries, leaving ∼7500 gene products yet to be confidently cataloged. We characterize these “PA-unseen” proteins in terms of tissue localization, transcript abundance, and Gene Ontology enrichment, and propose reasons for their absence from PeptideAtlas and strategies for detecting them in the future

The State of the Human Proteome in 2012 as Viewed through PeptideAtlas

The Human Proteome Project was launched in September 2010 with the goal of characterizing at least one protein product from each protein-coding gene. Here we assess how much of the proteome has been detected to date via tandem mass spectrometry by analyzing PeptideAtlas, a compendium of human derived LC–MS/MS proteomics data from many laboratories around the world. All data sets are processed with a consistent set of parameters using the Trans-Proteomic Pipeline and subjected to a 1% protein FDR filter before inclusion in PeptideAtlas. Therefore, PeptideAtlas contains only high confidence protein identifications. To increase proteome coverage, we explored new comprehensive public data sources for data likely to add new proteins to the Human PeptideAtlas. We then folded these data into a Human PeptideAtlas 2012 build and mapped it to Swiss-Prot, a protein sequence database curated to contain one entry per human protein coding gene. We find that this latest PeptideAtlas build includes at least one peptide for each of ∼12500 Swiss-Prot entries, leaving ∼7500 gene products yet to be confidently cataloged. We characterize these “PA-unseen” proteins in terms of tissue localization, transcript abundance, and Gene Ontology enrichment, and propose reasons for their absence from PeptideAtlas and strategies for detecting them in the future

The State of the Human Proteome in 2012 as Viewed through PeptideAtlas

The Human Proteome Project was launched in September 2010 with the goal of characterizing at least one protein product from each protein-coding gene. Here we assess how much of the proteome has been detected to date via tandem mass spectrometry by analyzing PeptideAtlas, a compendium of human derived LC–MS/MS proteomics data from many laboratories around the world. All data sets are processed with a consistent set of parameters using the Trans-Proteomic Pipeline and subjected to a 1% protein FDR filter before inclusion in PeptideAtlas. Therefore, PeptideAtlas contains only high confidence protein identifications. To increase proteome coverage, we explored new comprehensive public data sources for data likely to add new proteins to the Human PeptideAtlas. We then folded these data into a Human PeptideAtlas 2012 build and mapped it to Swiss-Prot, a protein sequence database curated to contain one entry per human protein coding gene. We find that this latest PeptideAtlas build includes at least one peptide for each of ∼12500 Swiss-Prot entries, leaving ∼7500 gene products yet to be confidently cataloged. We characterize these “PA-unseen” proteins in terms of tissue localization, transcript abundance, and Gene Ontology enrichment, and propose reasons for their absence from PeptideAtlas and strategies for detecting them in the future