Quantitative and integrative proteome analysis of peripheral nerve myelin identifies novel myelin proteins and candidate neuropathy loci.

[neuralgic amyotrophy]

Peripheral nerve myelin facilitates rapid impulse conduction and normal motor and sensory functions . Many aspects of myelin biogenesis , glia-axonal interactions , and nerve homeostasis are poorly understood at the molecular level . We therefore hypothesized that only a fraction of all relevant myelin proteins has been identified so far . Combining gel-based and gel-free proteomic approaches , we identified 545 proteins in purified mouse sciatic nerve myelin , including 36 previously known myelin constituents . By mass spectrometric quantification , the predominant P 0 , periaxin , and myelin basic protein constitute 21 , 16 , and 8 % of the total myelin protein , respectively , suggesting that their relative abundance was previously misestimated due to technical limitations regarding protein separation and visualization . Focusing on tetraspan-transmembrane proteins , we validated novel myelin constituents using immuno-based methods . Bioinformatic comparison with mRNA-abundance profiles allowed the categorization in functional groups coregulated during myelin biogenesis and maturation . By differential myelin proteome analysis , we found that the abundance of septin 9 , the protein affected in hereditary neuralgic amyotrophy , is strongly increased in a novel mouse model of demyelinating neuropathy caused by the loss of prion protein . Finally , the systematic comparison of our compendium with the positions of human disease loci allowed us to identify several candidate genes for hereditary demyelinating neuropathies . These results illustrate how the integration of unbiased proteome , transcriptome , and genome data can contribute to a molecular dissection of the biogenesis , cell biology , metabolism , and pathology of myelin .

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Diseases presenting "respectively" symptom

adrenal incidentaloma

allergic bronchopulmonary aspergillosis

alpha-thalassemia

benign recurrent intrahepatic cholestasis

carcinoma of the gallbladder

congenital adrenal hyperplasia

congenital diaphragmatic hernia

congenital toxoplasmosis

cushing syndrome

cystinuria

dedifferentiated liposarcoma

dentin dysplasia

dentinogenesis imperfecta

epidermolysis bullosa simplex

esophageal squamous cell carcinoma

familial hypocalciuric hypercalcemia

harlequin ichthyosis

hereditary cerebral hemorrhage with amyloidosis

hirschsprung disease

hodgkin lymphoma, classical

holt-oram syndrome

kallmann syndrome

lamellar ichthyosis

liposarcoma

neonatal adrenoleukodystrophy

neuralgic amyotrophy

oculocutaneous albinism

oligodontia

oral submucous fibrosis

pendred syndrome

pleomorphic liposarcoma

primary effusion lymphoma

proteus syndrome

pyruvate dehydrogenase deficiency

scrub typhus

triple a syndrome

von hippel-lindau disease

well-differentiated liposarcoma

wolf-hirschhorn syndrome

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