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Printable Handouts
Navigable Slide Index
- Introduction
- Research interests
- Learning objectives
- Overview of the glutamatergic synapse
- AMPARs and NMDARs
- PSD-95 identification
- PSD-95 structure
- The role of PSD-95 in NMDAR clustering
- Binding PSD-95 to endogenous NMDARs
- Evidence for the role of PSD-95 in postsynaptic NMDAR localization (1)
- Evidence for the role of PSD-95 in postsynaptic NMDAR localization (2)
- Evidence for the role of PSD-95 in postsynaptic AMPAR localization (1)
- Evidence for the role of PSD-95 in postsynaptic AMPAR localization (2)
- PSD-95: a central organizer of the postsynaptic site
- F-actin in dendritic spines
- α-actinin co-immunoprecipitates with PSD-95
- Kd124 reduces spine and synapse density
- Kd124 reduces synapse density but not content of NMDARs of remaining synapses
- Kd124 reduces content of PSD-95 in remaining synapses
- Kd124 does not reduce content of GluA1
- Kd124 does not reduce content of GluA2 or PSD-93
- Kd124 reduces mEPSC frequency but not amplitude
- Kd124 reduces synapse density but not content of glutamate receptors
- α-actinin binding to the N-terminus of PSD-95
- α-actinin binds to residues 1–13 of PSD-95
- PSD-95 predicted interactions with CH2 and CH1
- K10E and K11E mutations impair binding to α-actinin
- K10E and K11E mutations reduce postsynaptic PSD-95 accumulation
- K10E and K11E mutations reduce postsynaptic AMPAR accumulation (1)
- K10E and K11E mutations reduce postsynaptic AMPAR accumulation (2)
- E53K and E213K/D217K mutations
- In summary of these results
- Ca2+/CaM binding to PSD-95
- Ca2+/CaM binds to 13 N-terminal residues
- Ca2+/CaM binding and palmitoylation of PSD-95 (1)
- Ca2+/CaM binding and palmitoylation of PSD-95 (2)
- Y12E mutations affect Ca2+/CaM binding
- K10E, K11E and Y12E mutations affect binding
- Ca2+/CaM binding and palmitoylation of PSD-95 (3)
- Ca2+/CaM displaced PSD-95 from spines
- Ca2+/CaM displaced α-actinin from PSD-95
- Threonine 19 (T19) phosphorylation
- T19 phosphorylation augments and E17R decreases Ca2+/CaM binding
- Palmitoylation of PSD-95 is reduced upon induction of chemical LTD
- Abrogating Ca2+/CaM binding prevents depalmitoylation of PSD-95 during cLTD
- Abrogating Ca2+/CaM binding to PSD-95 prevents loss of surface AMPARs during cLTD
- Preventing depalmitoylation of PSD-95 during homeostatic synaptic downscaling
- Preventing loss of surface AMPARs during homeostatic synaptic downscaling
- Charge inversion mutations restore binding
- Charge inversion mutations restore downscaling (1)
- Charge inversion mutations restore downscaling (2)
- Charge inversion mutations restore downscaling (3)
- Ca2+/CaM regulates binding of PSD-95 to CDKL5
- Ca2+/CaM regulates binding of PSD-95 to α-actinin
- Ca2+ influx induces recruitment of Pyk2 by PSD-95
- PSD-95 links the beta-adrenergic receptor to the AMPAR complex
- Thank you for listening
Topics Covered
- PSD-95
- Structural proteins
- PSD-95 identification and structure
- Glutamatergic synapse
- PSD-95 anchors glutamate receptors
- Alpha-actinin anchors PSD-95
- AMPAR and NMDAR
- Alpha-actinin function and binding
- Ca2+/CaM binding to PSD-95
- Effect of Ca2+/CaM on PSD-95
- Palmitoylation/depalmitoylation cycle of PSD-95
- Long term depression (LTD)
- Homeostatic downscaling
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Talk Citation
Hell, J. (2022, July 31). PSD-95: dynamic localization of PSD-95 and glutamate receptors at postsynaptic sites [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved November 21, 2024, from https://doi.org/10.69645/OITC1112.Export Citation (RIS)
Publication History
Financial Disclosures
- Prof. Johannes Hell has not informed HSTalks of any commercial/financial relationship that it is appropriate to disclose.
PSD-95: dynamic localization of PSD-95 and glutamate receptors at postsynaptic sites
Published on July 31, 2022
43 min
A selection of talks on Neurology
Transcript
Please wait while the transcript is being prepared...
0:00
My name is Johannes Hill.
I am Professor of
Pharmacology at
University of California, Davis.
In addition, I'm vice chair of
pharmacology for
academic development,
the Departmental Mentoring
Director and the director
of our NH funded T32 training
program in pharmacology.
This training program focuses
on drug discovery
and development.
PSD-95, is one of the most
critical structural proteins
that organizes the
postsynaptic site
of synopsis in some
mammalian brain.
This presentation will provide
an in-depth overview of its
structure and function,
starting with the
discovery that it
interacts with postsynaptic
glutamate receptors.
0:42
My research interests
are focused
on the structural and functional
organizational of the
postsynaptic site
of glutamatergic synopsis.
We use biochemistry, including
structural analysis of proteins,
cell biology including
super-resolution microscopy.
Electrophysiology
including recording of
excitatory postsynaptic
currents or EPCs,
mini EPCs in single channels.
Behavior analysis,
which includes
memory and attention testing.
Framing key findings in
historical and
methodological context will
elucidate the discovery process
for people new to this field,
and perhaps makes
this presentation
inspiring and informative,
especially for my
younger colleagues.
1:29
Here's an overview of
the learning goals.
First, I will introduce
the basics of
neurotransmission and
glutamate receptors.
Then I will provide an overview
of some earlier work that
defined interactions of PSD-95
with glutamate receptors.
This overview will be
followed by a detailed
description of
the structural
aspects of binding of
the PDZ domains of PSD-95
to its target proteins.
These details remain highly
relevant and are widely
applicable to literally
hundreds of such interactions.
These biochemical aspects
will be followed by
the description of
how PSD-95 itself is
anchored at postsynaptic
sites and then up out
some specific functions of
PSD-95 beyond glutamate
receptor functions.
There is a second separate
talk that is focused on
the structural aspects of
the PDZ domain interactions.
As typical for
Henry Stewart talks,
most details are taken
from my own work,
but I will supplement with
some additional work by
others and provide appropriate
citations when indicated.
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