Aberrant expression of centractin and capping proteins, integral constituents of the dynactin complex, in fetal down syndrome brain.
Down syndrome (DS, trisomy 21) is the most frequent genetic cause of mental retardation. Although known for more than a hundred years the underlying pathomechanisms for the phenotype and impaired brain functions remain elusive. Performing protein hunting in fetal DS brain, we detected a series of cytoskeleton proteins with aberrant expression in fetal DS cortex. Fetal brain cortex samples of controls and DS of the early second trimenon of gestation were used for the experiments. We applied two-dimensional electrophoresis with in-gel digestion of protein spots, subsequent mass spectroscopical (MALDI) identification, and quantification of spots using specific software. Centractin alpha, F-actin capping protein alpha-1, alpha-2 and beta subunits were significantly reduced in fetal DS cortex, whereas dynein intermediate clear 2, dynein intermediate chain 2, and kinesin light chain protein levels were unchanged. Centractins and F-actin capping proteins are major determinants of the cytoskeleton and are involved in pivotal functions including cellular, organelle, and nuclear motility. Deranged centractins and F-actin capping proteins may represent or induce deficient axonal transport and may well contribute to deterioration of the cytoskeleton's mitotic functions in trisomy 21.
Gulesserian
Talin
T
Department of Pediatrics, University of Vienna, Waehringer Guertel 18, Vienna, A-1090, Austria.
Kim
Seong Hwan
SH
Fountoulakis
Michael
M
Lubec
Gert
G
D051339:Actin Depolymerizing Factors; D000199:Actins / Q000032:analysis / Q000378:metabolism*; D001921:Brain / Q000196:embryology / Q000378:metabolism* / Q000473:pathology; D001923:Brain Chemistry; D002540:Cerebral Cortex / Q000737:chemistry / Q000196:embryology / Q000378:metabolism; D051345:Destrin; D004314:Down Syndrome / Q000196:embryology / Q000378:metabolism*; D000072159:Dynactin Complex; D004398:Dyneins / Q000032:analysis / Q000096:biosynthesis; D015180:Electrophoresis, Gel, Two-Dimensional; D005260:Female; D005333:Fetus; D006801:Humans; D016547:Kinesins / Q000032:analysis / Q000096:biosynthesis; D008297:Male; D008840:Microfilament Proteins / Q000032:analysis / Q000378:metabolism*; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D021122:Protein Subunits; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D051339:Actin Depolymerizing Factors; D000199:Actins; D051345:Destrin; D000072159:Dynactin Complex; D008840:Microfilament Proteins; D008869:Microtubule-Associated Proteins; D021122:Protein Subunits; C076834:centractin; D004398:Dyneins; D016547:Kinesins