week 5 - CAMK2 autophosphorlyation Flashcards
WATCH FIRST 20 MINS OF THIS LECTURE#
maybe just watch the whole thing again? it went a bit fast for me
what is the role of CAMK2 autophosphylation?
Mayford et al (1996)
Mice express a transgene as well as endogenous gene. T286D mutation mimics autophosphorylation of alphaCaMK2
These mice also have impaired spatial learning
How to CAMK2 trangene expression levels link to LTP (Bejar et al, 2002)
When transgene expression levels are low, LTP is impaired
read more on this paper
What happens with alpha CamK2 point mutant mice (giese et al, 1998)
alphaCaMK2 point mutant mice have severely impaired CA1 LTP and memory formation
however, Cooke et al (2006) found that whilst this was the case in CA1, it was not in the case in the dentate gyrus
what does this mean for behaviour?
what did yasuda et al (2003)
during early life of the mice <10days old, CAMK2 is not needed for LTP, afterwards however it is
How important is CaMK2 autohphophorylation for learning and memory? (Need and Giese, 2003)
Very important. There is no spatial memory formation in T286A mutants
What is the conclusion from these studies?
this study shows that autophosphoryation is essential for induction of NMDA receptor-dependent potentiation in area CA1 and spatial memory formation
What is evidence against the CAMK22 hypothesis for memory storage?
Baurd et al, 2010)
CN21 is a peptide inhibitor which blocks camk2
When introduced before memory formation, it blocked learning, suggesting that camk2 is nessercary for formation
When introduced after formation, it did not block mainentence suggesting it is not nessercary for memory maintenence
Is LTP associated with persistent, autonomous CAMK2 activity? (fukunaga et al, 1993, chang et al 2017)
experiments are in conflict with each other.
Chang (2017) used imaging to look at this.
Found that in the dendritic spine, CAMK2 activity spikes but then decreases quickly after 20 seconds
what does this mean? watch the lecture again
Tullis et al 2023 - what is needed to get the assocation of campk2 and LTO
CAMK2 binding to glutamate receptor
Blocking kinase activity did not block ltp, but blocking binding to glu receptor did
The only kinase activity of ltp nessercary is the autophosphorylation
What is evidence for the CAMK2 hypothesis of memory storage (rossetti et al 2017)
Memory erasure hypothesis
By using a dominant negative blocker of CAMK2, k42M mutation makes CAMK2 inactive
Animals get rotated and learn not to get rotated into the danger zone
after use of the CAMK2 blocker, the memory was erased
This suggests that CAMK2 stores memory at the synapse (does it have a structural role there?)
What is the CAMK2 pathway at the synapse?
Look at slides or giese, neuropharmacology (2021)
are there intellectual disability diseases associated with CAMK2 point mutation?
Onori and van woerrden, 2021
Sequenced the unusal genome of severe intellectual disabilit patients
found patients had a camk2 point mutation
READING LIST
Elgersma et al (2004) Mouse genetic approaches to investigating CaMKII
function in plasticity and cognition. J Neurosci 24:8410-5.
Robison (2014) Emerging role of CaMKII in neuropsychiatric disease. Trends
Neurosci 37:653-62.
Giese and Mizuno (2013) The roles of protein kinases in learning and
memory. Learn Mem 20:540-52.
Lisman (2017). Criteria for identifying the molecular basis of the engram.
Mol. Brain 10:55.
Yasuda et al (2022). CaMKII as central molecular organizer of synaptic plasticity,
learning and memory. Nat. Rev. Neurosci. doi: 10.1038/s41583-022-00624-2
other molecule - PKmzeta
