| 1. |
- Harvey, K, et al.
(författare)
-
The GDP-GTP exchange factor collybistin: An essential determinant of neuronal gephyrin clustering
- 2004
-
Ingår i: The Journal of Neuroscience. - 1529-2401. ; 24:25, s. 5816-5826
-
Tidskriftsartikel (refereegranskat)abstract
- Glycine receptors (GlyRs) and specific subtypes of GABA(A) receptors are clustered at synapses by the multidomain protein gephyrin, which in turn is translocated to the cell membrane by the GDP-GTP exchange factor collybistin. We report the characterization of several new variants of collybistin, which are created by alternative splicing of exons encoding an N-terminal src homology 3 (SH3) domain and three alternate C termini (CB1, CB2, and CB3). The presence of the SH3 domain negatively regulates the ability of collybistin to translocate gephyrin to submembrane microaggregates in transfected mammalian cells. Because the majority of native collybistin isoforms appear to harbor the SH3 domain, this suggests that collybistin activity may be regulated by protein-protein interactions at the SH3 domain. We localized the binding sites for collybistin and the GlyR beta subunit to the C-terminal MoeA homology domain of gephyrin and show that multimerization of this domain is required for collybistin-gephyrin and GlyR-gephyrin interactions. We also demonstrate that gephyrin clustering in recombinant systems and cultured neurons requires both collybistin-gephyrin interactions and an intact collybistin pleckstrin homology domain. The vital importance of collybistin for inhibitory synaptogenesis is underlined by the discovery of a mutation (G55A) in exon 2 of the human collybistin gene (ARHGEF9) in a patient with clinical symptoms of both hyperekplexia and epilepsy. The clinical manifestation of this collybistin missense mutation may result, at least in part, from mislocalization of gephyrin and a major GABA(A) receptor subtype.
|
|
| 2. |
|
|
| 3. |
- Garpenstrand, H, et al.
(författare)
-
A regulatory monoamine oxidase a promoter polymorphism and personality traits
- 2002
-
Ingår i: Neuropsychobiology. - : S. Karger AG. - 0302-282X .- 1423-0224. ; 46:4, s. 190-193
-
Tidskriftsartikel (refereegranskat)abstract
- Monoamine oxidase type A (MAOA) has been implicated to be part of mechanisms underlying human temperament and psychiatric disorders. We hypothesised that a functional polymorphism in the 5′ untranslated region of the MAOA gene is associated with specific personality traits. In 371 healthy Caucasians, we estimated personality traits by the use of the Karolinska Scales of Personality (KSP), Scandinavian Universities Scales of Personality, Health-Relevant 5-Factor Personality inventory, Temperament and Character Inventory and the revised NEO Personality Inventory. In the same subjects, we analysed the genotype of a polymorphic region consisting of a variable number of a 30-bp repeat sequence located approximately 1.2 kb upstream of the MAOA gene. After correction for multiple testing, no statistically significant differences between MAOA genotype and personality were observed in men (n = 206) nor in women (n = 165). We conclude that the structure of this MAOA promoter region does not have a large impact on the expression of personality characteristics in the present Swedish population.
|
|
| 4. |
|
|
| 5. |
|
|
| 6. |
|
|
| 7. |
|
|
| 8. |
|
|
| 9. |
|
|
| 10. |
- Zammit, S, et al.
(författare)
-
Paternal age and risk for schizophrenia
- 2003
-
Ingår i: The British journal of psychiatry : the journal of mental science. - : Royal College of Psychiatrists. - 0007-1250. ; 183, s. 405-408
-
Tidskriftsartikel (refereegranskat)abstract
- Previously reported associations between advancing paternal age and schizophrenia could be due to an increase in paternal germ cell mutations or be confounded by heritable personality traits associated with schizophrenia that result in delayed parenthood.AimsTo investigate this association while adjusting for personality traits related to poor social integration in the subjects.MethodA cohort of 50 087 adolescent males was followed up by record linkage to determine hospital admissions for schizophrenia between 1970 and 1996.ResultsAdvancing paternal age was associated with an increased risk of developing schizophrenia in a ‘dose-dependent’ manner. The adjusted odds ratio for each 10-year increase in paternal age was 1.3 (95% Cl 1.0–1.5; P=0.015).ConclusionsAdvancing paternal age is an independent risk factor for schizophrenia. Adjusting for social integration in subjects made little difference to this association, consistent with the hypothesis that advancing paternal age may increase liability to schizophrenia owing to accumulating germ cell mutations.
|
|
