Gephyrin palmitoylation and oligomerization in synaptic plasticity, membrane recruitment and proteostasis:
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1. Verfasser: | |
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Format: | Abschlussarbeit Buch |
Sprache: | English |
Veröffentlicht: |
2012
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Schlagworte: | |
Online-Zugang: | Inhaltsverzeichnis |
Beschreibung: | Zsfassung in dt. und engl. Sprache |
Beschreibung: | 147 S. Ill., graph. Darst. |
Internformat
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Datensatz im Suchindex
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adam_text | Titel: Gephyrin palmitoylation and oligomerization in synaptic plasticity, membrane recruitment and proteos
Autor: Dejanović, Borislav
Jahr: 2012
Table of contents
1 Introduction_____________________________________________________3
1.1 Synaptic transmission_____________________________________________3
1.2 Synaptic inhibition________________________________________________. 4
1.3 Structure and function of glycine and GABA receptors__________________ 5
1.4 Postsynaptic density______________________________________________6
1.5 Gephyrin________________________________________________________7
1.5.1 Clustering of inhibitory receptors at synapses________________________7
1.5.2 Synaptic plasticity at inhibitory synapses___________________________10
1.5.3 Protein and gene structure of gephyrin____________________________11
1.5.4 Clustering of gephyrin_______________________________________13
1.5.5 Gephyrin interacting proteins___________________________________14
1.5.6 Post-translational modification of gephyrin_________________________15
1.6 Palmitoylation__________________________________________________ 16
1.6.1 Palmitoyl acyl transferases____________________________________18
1.6.2 Protein depalmitoytation______________________________________21
1.7 S-nitrosylation__________________________________________________22
1.8 Gephyrin in disease______________________________________________23
1.9 Aims of study ___________________________________________25
2 Results________________________________________________________26
2.1 Gephyrin is membrane associated In vivo____________________________26
2.2 Gephyrin is paimitoylated_________________________________________29
2.3 Gephyrin palmitoylation triggers membrane association________________32
2.4 Gephyrin palmitoylation is essential for proper synapse targeting and
GABAergic synapse assembly______________________________________33
2.5 Gephyrin palmitoylation is regulated by synaptic strength_______________37
2.6 Palmitoylation influences gephyrin stability and regulates the amount of
synaptic gephyrin_______________________________________________38
2.6.1 Palmitoylation does not modify biophysical parameters of gephyrin but influences
proteolytic degradation_______________________________________41
2.7 Identification of gephyrin palmitoylatlng enzymes_____________________44
2.7.1 Gephyrin can be palmitoylated by several palmitoyl transferases in non-neuronal
cells___________________________________________________44
2.7.2 Presence of DHHC proteins does not modify gephyrin blob formation_______46
2.7.3 DHHC12 and 16 modulate gephyrin cluster size and intensity in cultured
hippocampal neurons________________________________________48
2.7.4 Distinct subcellular localization of DHHC12 and 16 in neuronal cells________50
2.7.5 Gephyrin co-localizes with DHHC12 in neurites______________________52
2.7.6 Gephyrin forms complexes with DHHC12 and 16_____________________54
2.7.7 Inactive palmitoyl transferase mutants block gephyrin palmitoylation in
heterologous cells__________________________________________55
2.8 Identification of palmitoylated cysteine residues_______________________56
2.9 Age-related gephyrin palmitoylation_________________________________60
2.10 Regulation of gephyrin depalmitoylation_____________________________60
2.10.1 Gephyrin is nitrosylated in vivo_________________________________61
2.10.2 Nitrosylation competes with palmitoylation on gephyrin________________62
2.10.3 Gephyrin interacts with nNOS_________________________________64
2.10.4 Quantification of palmitoylated protein in vivo_______________________65
2.1 Heterozygous gephyrin truncation in a patient with idiopathic generalized
epilepsy________________________________________________________67
3 Discussion_____________________________________________________76
3.1 Gephyrin is membrane-associated_________________________________76
3.2 Gephyrin palmitoylation__________________________________________79
3.2.1 Gephyrin palmitoylation regulates its localization at inhibitory synapses_____82
3.2.2 Gephyrin palmitoylation is regulated by synaptic activity________________84
3.2.3 Palmitoylation-dependent gephyrin turnover________________________85
3.2.4 DHHC12 and DHHC16 are gephyrin palmitoylating transferases__________88
3.3 Gephyrin nitrosylation competes with palmitoylation___________________91
3.4 Gephyrin palmitoylation sites______________________________________95
3.5 Age-dependent gephyrin palmitoylation______________________________96
3.6 Heterozygous gephyrin truncation in a patient with idiopathic generalized
epilepsy________________________________________________________97
4 Materials and methods_________________________________________102
4.1 Materials______________________________________________________ 102
4.2 Molecular biological methods____________________________________104
4.3 General methods_______________________________________________107
4.4 Protein expression, cell transection and immunostaining______________108
4.5 Biochemical methods___________________________________________111
4.6 Biophysical methods____________________________________________120
5 Appendix_____________________________________________________121
6 References____________________________________________________124
7 Acknowledgment______________________________________________144
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author_facet | Dejanović, Borislav 1983- |
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ctrlnum | (OCoLC)914847097 (DE-599)HBZHT017515220 |
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spelling | Dejanović, Borislav 1983- Verfasser (DE-588)1029912785 aut Gephyrin palmitoylation and oligomerization in synaptic plasticity, membrane recruitment and proteostasis vorgelegt von: Borislav Dejanović 2012 147 S. Ill., graph. Darst. txt rdacontent n rdamedia nc rdacarrier Zsfassung in dt. und engl. Sprache Köln, Univ., Diss., 2012 (DE-588)4113937-9 Hochschulschrift gnd-content HBZ Datenaustausch application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=025973921&sequence=000002&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis |
spellingShingle | Dejanović, Borislav 1983- Gephyrin palmitoylation and oligomerization in synaptic plasticity, membrane recruitment and proteostasis |
subject_GND | (DE-588)4113937-9 |
title | Gephyrin palmitoylation and oligomerization in synaptic plasticity, membrane recruitment and proteostasis |
title_auth | Gephyrin palmitoylation and oligomerization in synaptic plasticity, membrane recruitment and proteostasis |
title_exact_search | Gephyrin palmitoylation and oligomerization in synaptic plasticity, membrane recruitment and proteostasis |
title_full | Gephyrin palmitoylation and oligomerization in synaptic plasticity, membrane recruitment and proteostasis vorgelegt von: Borislav Dejanović |
title_fullStr | Gephyrin palmitoylation and oligomerization in synaptic plasticity, membrane recruitment and proteostasis vorgelegt von: Borislav Dejanović |
title_full_unstemmed | Gephyrin palmitoylation and oligomerization in synaptic plasticity, membrane recruitment and proteostasis vorgelegt von: Borislav Dejanović |
title_short | Gephyrin palmitoylation and oligomerization in synaptic plasticity, membrane recruitment and proteostasis |
title_sort | gephyrin palmitoylation and oligomerization in synaptic plasticity membrane recruitment and proteostasis |
topic_facet | Hochschulschrift |
url | http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=025973921&sequence=000002&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |
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