Vertiefung Physiologie & Pathophysiologie at ETHZ - ETH Zurich

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WICHTIGSTE PUNKTE (4)

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Cam Kinase 2 Infos

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Actinomycin D

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Conclusion    III


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Was macht c-fos?

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What is required to form long-lasting forms of synaptic plasticity?

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Zu was ist transcriptional regulation coupled?

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Was ist das Rett Syndrom?

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microRNA target regulation


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Which mutations are associated with schizophrenia?


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What is BDNF?

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Anisomycin

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Vertiefung Physiologie & Pathophysiologie

WICHTIGSTE PUNKTE (4)

  • neuronale Aktivität stimuliert Genexpression at the level of transcription
  • Stimulation wird durch Ca2+ abhängigen, sowie MAPK signaling cascades zum Nukleus weitergeleitet
  • Spezifische Transkriptionsfaktoren (CREB, MEF2, MeCP2) regulieren die Expression von downstram Genen, welche im Synapsen-Umbau involviert sind
  • Mutationen in signaling Komponenten führen zu neurological disorders (autism, depression, epilepsy, ...)

Vertiefung Physiologie & Pathophysiologie

Cam Kinase 2 Infos

Struktur: 12 Kopien of the enzyme, assembled to a stacked pair of rings, with kinase domains on the outside linked to a central hub: this structure --> function as memory device


switching to active state when exposed to Ca2+/Calmodulin

once activated it stays active, even when Ca2+ signal has decayed.

Vertiefung Physiologie & Pathophysiologie

Actinomycin D

= Blocker der Transkription

Vertiefung Physiologie & Pathophysiologie

Conclusion    III


• Non-coding RNAs represent the vast majority of the cellular transcriptome
• miRNAs are small non-coding RNAs that act as
negative regulators of mRNA translation
• miRNAs play important roles in neural circuit
development and synaptic plasticity
• miRNAs are mutated or deregulated in
neurological disorders
• Research on other non-coding RNAs (lncRNAs,
circRNAs) is still in its infancy


Vertiefung Physiologie & Pathophysiologie

Was macht c-fos?

(c-fos = Teil eines Transkriptionsfaktor AP1, sowie Proto-onkogen)


  • führt zu Phosphorylation von CREB, sowie SRF(=Transkriptionsfaktoren)
  • Rekrutieren von Co-Aktivatoren (Elk, CBP)
  • Aktivierung von klassischen immediate-early genes (oft auch TFs wie z.B. c-fos, c-jun, egr-1,...)





Vertiefung Physiologie & Pathophysiologie

What is required to form long-lasting forms of synaptic plasticity?

New transcription and translation of mRNA

Vertiefung Physiologie & Pathophysiologie

Zu was ist transcriptional regulation coupled?

zu Synapsen-umbau (=remodeling)

  • Aktivität stimuliert MEF2
  • Synthese von Arc (endocytose) und Ube3a (Proteinabbau) ist erhöht
  • AMPAR Internalisierung wird fine getuned
  • fehlerhaft, wenn Ube3a abwesend ist und somit nich Arc degradieren kann. Dies führt zu weniger Synapsen. --> Angelman Syndrom (=Autismusart)

Vertiefung Physiologie & Pathophysiologie

Was ist das Rett Syndrom?

  • rare ( 1:10000), X-linked neurodevelopmental disorder, mostly affecting females (Weil Männer aufgrund des mangelnden Backup X gar nicht erst zur Welt kommen)
  • Mutation im MeCP2 gen
  • zuerst normale frühe Entwicklung (up to 3 years), danach Stagnation und Regression von kognitiven Fähigkeiten wie z.B. der Sprache
  • Andere Symptome sind: seizure, motorische Schwierigkeiten, Skoliose, Schlafprobleme
  • Aktuell ist keine Kur oder pharmalogische Therapie verfügbar

Vertiefung Physiologie & Pathophysiologie

microRNA target regulation


• miRNAs bind target mRNAs within
mi RISC by imperfect complementarity in
the 3’UTR
• The miRNA “seed” region is crucial of
target recognition
• miRNAs repress target expression by a
combination of translational blockade and
mRNA decay
• miRNA activity can be regulated by
external stimuli and RBPs


Vertiefung Physiologie & Pathophysiologie

Which mutations are associated with schizophrenia?


Mutations in miR-137


Vertiefung Physiologie & Pathophysiologie

What is BDNF?

a late-response gene, which is involved in the regulation of synapse function.

--> neurotropic peptide

--> released upon activity

--> binds to Trk receptors

--> affects synapse function by multiple mechanisms


„brain derived neurotropic factor“

Vertiefung Physiologie & Pathophysiologie

Anisomycin

= Blocker der mRNA translation

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