ABSTRACT
Quaking (QKI) is a gene exclusively expressed within glial cells. QKI has previously been implicated in various neurological disorders and diseases, including Alzheimer's disease (AD), a condition for which increasing evidence suggests a central role of glia cells. The objective of the present study was to investigate the expression levels of QKI and three QKI isoforms (QKI5, QKI6, and QKI7) in AD. Genes that have previously been related to the ontogeny and progression of AD, specifically APP, PSEN1, PSEN2, and MAPT, were also investigated. A real-time PCR assay of 123 samples from human postmortem sporadic AD patients and control brains was performed. The expression values were analyzed with an analysis of covariance model and subsequent multiple regressions to explore the possibility of related expression values between QKI, QKI isoforms, and AD-related genes. Further, the sequences of AD-related genes were analyzed for the presence of QKI binding domains. QKI and all measured QKI isoforms were found to be significantly upregulated in AD samples, relative to control samples. However, APP, PSEN1, PSEN2, and MAPT were not found to be significantly different. QKI and QKI isoforms were found to be predictive for the variance of APP, PSEN1, PSEN2, and MAPT, and putative QKI binding sites suggests an interaction with QKI. Overall, these results implicate a possible role of QKI in AD, although the exact mechanism by which this occurs remains to be uncovered.
Subject(s)
Alzheimer Disease , Brain/metabolism , Neurofibrillary Tangles/genetics , Plaque, Amyloid/genetics , RNA-Binding Proteins/metabolism , Up-Regulation/genetics , Age Factors , Alzheimer Disease/genetics , Alzheimer Disease/metabolism , Alzheimer Disease/pathology , Amyloid beta-Protein Precursor/genetics , Amyloid beta-Protein Precursor/metabolism , Analysis of Variance , Female , Humans , Linear Models , Male , Mutation/genetics , Presenilin-1/genetics , Presenilin-1/metabolism , Presenilin-2/genetics , Presenilin-2/metabolism , Protein Isoforms/genetics , Protein Isoforms/metabolism , RNA, Messenger/metabolism , RNA-Binding Proteins/genetics , tau Proteins/metabolismABSTRACT
Quaking (QKI) is an RNA-binding protein involved in post-transcriptional mRNA processing. This gene is found to be associated with several human neurological disorders. Early expression of QKI proteins in the developing mouse neuroepithelium, together with neural tube defects in Qk mouse mutants, suggest the functional requirement of Qk for the establishment of the nervous system. As a knockout of Qk is embryonic lethal in mice, other model systems like the zebrafish could serve as a tool to study the developmental functions of qki. In the present study we sought to characterize the evolutionary relationship and spatiotemporal expression of qkia, qki2, and qkib; zebrafish homologs of human QKI. We found that qkia is an ancestral paralog of the single tetrapod Qk gene that was likely lost during the fin-to-limb transition. Conversely, qkib and qki2 are orthologs, emerging at the root of the vertebrate and teleost lineage, respectively. Both qki2 and qkib, but not qkia, were expressed in the progenitor domains of the central nervous system, similar to expression of the single gene in mice. Despite having partially overlapping expression domains, each gene has a unique expression pattern, suggesting that these genes have undergone subfunctionalization following duplication. Therefore, we suggest the zebrafish could be used to study the separate functions of qki genes during embryonic development.
Subject(s)
RNA-Binding Proteins/genetics , Zebrafish Proteins/genetics , Zebrafish/genetics , Amino Acid Sequence , Animals , Base Sequence , Biological Evolution , Chordata/anatomy & histology , Chordata/genetics , Conserved Sequence , Evolution, Molecular , Extremities/embryology , Gene Expression Regulation, Developmental , Humans , In Situ Hybridization, Fluorescence , Mice , Molecular Sequence Data , Nerve Tissue Proteins/biosynthesis , Nerve Tissue Proteins/genetics , Nervous System/embryology , Nervous System/metabolism , Neural Tube/metabolism , Phylogeny , RNA-Binding Proteins/biosynthesis , Real-Time Polymerase Chain Reaction , Sequence Alignment , Sequence Homology , Species Specificity , Synteny , Zebrafish/embryology , Zebrafish/metabolism , Zebrafish Proteins/biosynthesisABSTRACT
OBJECTIVE: Bimanual movements are a fundamental motor skill. Whereas substantial research is available from right-handers, much less is known from left-handers. Accordingly, in the present electroencephalography (EEG) study we evaluated bimanual behavior in left- versus right-handers. METHOD: Thirteen left-handers and 13 right-handers took part in the experiment. Cortical dynamics were evaluated by means of EEG coherence in the beta frequency band (14-28 Hz), and behavioral performance was measured using motor error. RESULTS: The EEG data revealed that right-handers showed a left-sided lateralization pattern whereas left-handers demonstrated a bilateral organization pattern during symmetrical actions. Asymmetry of the bimanual task demands modified the hemispheric profile for both groups and resulted in an additional involvement of the motor-nondominant hemisphere. Brain-behavioral correlations underlined that response planning strongly relied on the left hemisphere irrespective of handedness whereas the motor-dominant hemisphere drove response execution. CONCLUSION: The findings suggest that skilled motor planning may develop preferentially in the left hemisphere.
