Aberrant expression of signaling-related proteins 14-3-3 gamma and RACK1 in fetal Down Syndrome brain (trisomy 21)

• Published in: Electrophoresis Vol. 23; no. 1; pp. 152 - 157
• Main Authors: Peyrl, Andreas, Weitzdoerfer, Rachel, Gulesserian, Talin, Fountoulakis, Michael, Lubec, Gert
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag GmbH 01.01.2002; WILEY‐VCH Verlag GmbH
• Subjects: 14-3-3 gamma; 14-3-3 Proteins; Arabidopsis Proteins - analysis; Brain - embryology; Brain - metabolism; cAMP-dependent protein kinase type II; Case-Control Studies; Cyclic AMP-Dependent Protein Kinase Type II; Cyclic AMP-Dependent Protein Kinases - analysis; Down Syndrome; Down Syndrome - metabolism; Electrophoresis, Gel, Two-Dimensional; Female; Fetus - abnormalities; Fetus - metabolism; Gene Expression Regulation, Developmental; Humans; Male; MAP Kinase Signaling System; Mitogen-activated protein kinase I; RACK1; Receptors for Activated C Kinase; Receptors, Cell Surface - analysis; Receptors, Cell Surface - metabolism; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Tyrosine 3-Monooxygenase - analysis; Tyrosine 3-Monooxygenase - metabolism
• ISSN: 0173-0835; 1522-2683
• DOI: 10.1002/1522-2683(200201)23:1<152::AID-ELPS152>3.0.CO;2-T

Although Down Syndrome (DS, trisomy 21) is the most frequent isolated cause of mental retardation, information on brain protein expression and in particular protein expression of signaling‐related proteins is limited. Impaired signaling in DS involving different signaling systems has been proposed and the availability of fetal brain along with recent proteome technologies unambiguously identifying individual brain proteins made us study individual signaling factors in the brain. We studied fetal brain cortex of controls (n = 7) and DS (n = 9) from early second trimester of gestation by two‐dimensional gel electrophoresis with subsequent matrix‐assisted laser/desorption ionization (MALDI) identification followed by quantification with specific software. Four 14‐3‐3 protein isoforms, mitogen‐activated protein kinase 1, receptor for activited kinase 1 (RACK1), constitutive photomorphogenesis (COP9) complex subunit 4 and cAMP‐dependent protein kinase type II have been identified. Quantification showed that protein 14‐3‐3 gamma (means ± standard deviation of controls: 10.18 ± 2.30 and of DS 4.20 ± 1.19) and two spots assigned to RACK1 (controls spot 1: 4.15 ± 2.45 and DS 1.95 ± 0.93; controls spot 2: 5.08 ± 2.4 vs. DS: 2.56 ± 1.19) were significantly decreased in DS cortex. Reduced 14‐3‐3 gamma may represent impaired neuronal differentiation, synaptic plasticity and impaired signaling by PKC and Raf while decreased RACK1 (anchoring protein receptor for activated C‐kinase) may reflect or generate deranged beta‐II‐ protein kinease C (PKC) function with the putative biological meaning of aberrant migration and neuritic outgrowth in DS early in life.