title: Neuronal localization of the mitochondrial protein NIPSNAP1 in rat nervous system.
abstract: The NIPSNAP (4-nitrophenylphosphatase domain and non-neuronal SNAP25-like protein homolog 1) proteins belong to a highly conserved family of proteins of unknown function. We found that NIPSNAP1 binds to the branched-chain alpha-keto acid (BCKA) dehydrogenase enzyme complex, which is disrupted in maple syrup urine disease, a disease of branched-chain amino acid catabolism that results in neurological dysfunction. Phenylketonuric (PKU) and epileptic mice show altered expression of NIPSNAP1 in the brain. Therefore, the distribution and localization of NIPSNAP1 in rat brain was determined. Results show that NIPSNAP1 is expressed exclusively in neurons including pyramidal neurons in the cerebral cortex, Purkinje neurons in the cerebellum and motor neurons in the spinal cord. Dopaminergic neurons in midbrain and noradrenergic neurons in the brainstem, which are affected in PKU, also express NIPSNAP1. NIPSNAP1 is found to be localized in the mitochondrial matrix and can bind dihydrolipoyl-transacylase and -transacetylase components of the BCKA and pyruvate dehydrogenase complexes in vitro. Our data provide the first experimental evidence for a strictly neuronal expression of this mitochondrial protein in the rat nervous system.
authors.affiliation: Department of Biochemistry, Wake Forest University School of Medicine, Medical Center Blvd, Winston-Salem, NC, USA.
authors.forename: Manisha
authors.initials: M
authors.lastname: Nautiyal
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Sweatt
authors.forename: James A
authors.initials: JA
authors.lastname: MacKenzie
authors.forename: R
authors.initials: R
authors.lastname: Mark Payne
authors.forename: Sylvia
authors.initials: S
authors.lastname: Szucs
authors.forename: Reuben
authors.initials: R
authors.lastname: Matalon
authors.forename: Reidar
authors.initials: R
authors.lastname: Wallin
authors.forename: Susan M
authors.initials: SM
authors.lastname: Hutson
mesh_terms: D000818:Animals; D001921:Brain / Q000033:anatomy & histology / Q000378:metabolism; D005260:Female; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D008375:Maple Syrup Urine Disease / Q000378:metabolism; D008565:Membrane Proteins; D051379:Mice; D008817:Mice, Mutant Strains; D008928:Mitochondria / Q000201:enzymology / Q000648:ultrastructure; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009420:Nervous System / Q000033:anatomy & histology / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D010661:Phenylketonurias / Q000378:metabolism; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; C553730:NIPSNAP1 protein, rat; D009419:Nerve Tissue Proteins; C485133:Nipsnap1 protein, mouse; D011506:Proteins