title: Proteomic assessment of sympathetic ganglia from adult mice that possess null mutations of ExonIII or ExonIV in the p75 neurotrophin receptor gene.
abstract: Neurotrophins, such as nerve growth factor (NGF), are capable of binding to the transmembrane p75 neurotrophin receptor (p75NTR), which regulates a variety of cellular responses including apoptosis and axonal elongation. While the development of mutant mouse strains that lack functional p75NTR expression has provided further insight into the importance of this neurotrophin receptor, there remains a paucity of information concerning how the loss of p75NTR expression may alter neural phenotypes. To address this issue, we assessed the proteome of the cervical sympathetic ganglia from two mutant lines of mice, which were compared to the ganglionic proteome of age-matched wild type mice. The ganglionic proteome of mice possessing two mutant alleles of either exonIII or exonIV for the p75NTR gene displayed detectable alterations in levels of Lamin A, tyrosine hydroxylase, and Annexin V, as compared to ganglionic proteome of wild type mice. Decreased expression of the basic isoform of tyrosine hydroxylase may be linked to perturbed NGF signaling in the absence of p75NTR in mutant mice. Stereological measurement showed significant increases in the number of sympathetic neurons in both lines of p75NTR-deficient mice, relative to wild type mice. This enhanced survival of sympathetic neurons coincides with shifts toward the more basic isoforms of Annexin V in mutant mice. This study, in addition to providing the first comparative proteomic assessment of sympathetic ganglia, sheds new light onto the phenotypic changes that occur as a consequence of a loss of p75NTR expression in adult mice.
authors.affiliation: Centre for Neuroscience Studies, Queen's University, Kingston, ON, Canada.
authors.forename: Todd G
authors.initials: TG
authors.lastname: McDonald
authors.forename: Samuel A
authors.initials: SA
authors.lastname: Scott
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Kane
authors.forename: Michael D
authors.initials: MD
authors.lastname: Kawaja
mesh_terms: D000818:Animals; D017304:Annexin A5 / Q000378:metabolism; D015536:Down-Regulation; D010450:Endopeptidases / Q000378:metabolism; D005728:Ganglia, Sympathetic / Q000378:metabolism* / Q000473:pathology; D006360:Heat-Shock Proteins / Q000378:metabolism; D007527:Isoenzymes / Q000378:metabolism; D034904:Lamin Type A / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D024101:Mitochondrial Proteins / Q000378:metabolism; D009124:Muscle Proteins / Q000378:metabolism; D009154:Mutation; D009474:Neurons / Q000378:metabolism; D010641:Phenotype; D020543:Proteome / Q000235:genetics*; D040901:Proteomics; D017475:Receptors, Nerve Growth Factor / Q000235:genetics* / Q000378:metabolism*; D015203:Reproducibility of Results; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D064570:Ubiquitin-Specific Proteases
chemical_list: D017304:Annexin A5; D006360:Heat-Shock Proteins; D007527:Isoenzymes; D034904:Lamin Type A; D024101:Mitochondrial Proteins; D009124:Muscle Proteins; D020543:Proteome; D017475:Receptors, Nerve Growth Factor; C517634:Ngfr protein, mouse; C532603:mitofilin protein, mouse; D014446:Tyrosine 3-Monooxygenase; D010450:Endopeptidases; D064570:Ubiquitin-Specific Proteases