INTRODUCTON

HISTORY

IMPORTANCE

SUBJECT MATTER

SUMMARY

REFERENCES

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Nerve cell membranes are the

communication centers of the brain. 

It is through membrane processes that

nerve cells communicate with one

another and also turn on/off or up/down

regulate cell genome activity. 

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Alzheimer’s disease

Autism

chronic alcoholism

Major depressive disorder

schizophrenia. 

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LOCATION PHOSPHATIDYL CHOLINE

PHOSPHOTIDYL ETHANOLOMINE

SPHINOMYELIN

CHOLESTEROL

RBC 21 29 21 26

NEURON 16 37 13 34

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Membranes are composed of two major classes of molecules –

lipids

proteins

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phospholipids  

Glycolipids

Sphingolipids

cholesterol

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Integral membrane

Lipid anchored

Peripheral

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The most common type of IMP is the transmembrane protein (TM)

Protein cross the membrane only once or it may weave in and out, crossing several times.

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IMPs include

transporters,

channels,

receptors,

enzymes,

structural membrane-anchoring domains,

proteins involved in accumulation and transduction of energy, and proteins responsible for cell adhesion.

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Insulin receptor Some types of cell adhesion proteins or cell

adhesion molecules (CAMs) such as Integrins, Cadherins, NCAMs, or Selectins.

Some types of receptor proteins

Glycophorin

Rhodopsin

Band 3

CD36

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TM proteins can be categorized as

Type I, amino-terminus is outside of the membrane,

Type II, which have their carboxy-terminus outside of the membrane.

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1. a single transmembrane α-helix (bitopic membrane protein) 2. a polytopic α-helical protein 3. a transmembrane β barrel

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Peripheral membrane proteins are proteins that adhere only temporarily to the biological membrane

Interact with integral membrane protein

Communicate cell interior to cell external

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In lipid anchored proteins, a covalently attached fatty acid such as palmitate or myristate serves to anchor them to either face of the cell membrane.

Examples

G proteins

certain kinases. 04/10/23 18nerve membranes

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The postsynaptic density (PSD) is a cytoskeleton specialization at neuronal synapses

Identified as an electron-dense region at the membrane of a postsynaptic neuron

PSDs are usually composed of L-glutamate neurotransmitter receptors,

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Their molecular scaffolding molecules,

Cell adhesion molecules ,diverse set of other signaling proteins.

PSDs vary in size and composition among brain regions

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An analysis was made of the protein composition of a fraction of postsynaptic densities (PSDs) prepared from rat brain.

Protein makes up 90% of the material in the PSD fraction.

Two major polypeptide fractions are present, based on sodium dodecyl sulfate polyacrylamide gel electrophoresis.

The major polypeptide fraction has a molecular weight of 53,000, makes up about 45% of the PSD protein, and comigrates on gels with a major polypeptide of the synaptic plasma membrane.

The other polypeptide band has a molecular weight of 97,000, accounts for 17% of the PSD protein, and is not a prominent constituent of other fractions.

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The postsynaptic density (PSD) is crucial for synaptic functions

Homer and Shank are among the most abundant scaffolding proteins in the PSD, working synergistically for maturation of dendritic spines.

Homer and Shank, together, form a mesh-like matrix structure..

Homer-Shank complex serves as a structural framework and as an assembly platform for other PSD proteins.

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Six other polypeptides of higher molecular weight (100,000–180,000) are consistently present in small amounts (3–9% each).

The PSD fraction contains slightly greater amounts of polar amino acids and proline than the synaptic plasma membrane fraction, but no amino acid is usually prominent.

The PSD apparently consists of a structural matrix formed primarily by a single polypeptide or class of polypeptides of 53,000 molecular weight.

Small amounts of other specialized proteins are contained within this matrix

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ErbB4 interacts specifically with the first and second PDZ domains of postsynaptic density (PSD) protein 95 (PSD95), a scaffold protein, and is localized in the PSD of excitatory synapses.

The interaction with PSD95 enhances neuregulin 1 (NRG1) signalling, presumably by increasing ErbB4 homodimerization.

NRG1, by activating ErbB4, suppresses long-term potentiation induction and expression.

Through PSD95, ErbB4 signalling might regulate the properties of NMDA (N-methyl-D-aspartate) receptors (NMDARs), AMPA (-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) receptors (AMPARs) and K+ channels (K+ ch).

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Through the GKAP–Shank–Homer complex, ErbB4 signalling might be involved in regulating the function of metabotropic glutamate receptors (mGluRs).

PSD95 might also recruit ErbB4 to the neuroligin–neurexin complex that is essential for synapse formation

ErbB2, on the other hand, interacts with erbin, a protein that contains multiple leucine-rich domains and a PDZ domain

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This interaction has been implicated in regulating NRG1 signalling

ErbB4 is present in the presynaptic terminals of GABA (-aminobutyric acid )-ergic interneurons

NRG1 stimulates presynaptic ErbB4 to enhance activity-dependent GABA release through mechanisms that have yet to be identified.

A working hypothesis for how NRG1 might regulate pyramidal neuron activity.

The output of pyramidal neurons in the prefrontal cortex (PFC) is regulated by excitatory glutamatergic neurons (shown in red) and various inhibitory GABAergic interneurons (shown in green).

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NRG1 regulates glutamatergic transmission and/or plasticity by activating PSD-localized ErbB4.

There are at least three types of GABAergic interneurons in the PFC.

Wide-arbor basket cells target the somata and proximal dendrites of pyramidal neurons and adjust the integrated synaptic response.

Chandelier cells (or axon-targeting interneurons) terminate at or near the axon hillock of pyramidal neurons, forming vertical arrays of terminals termed 'cartridges', to regulate the generation and timing of action potentials.

.

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Conversely, Martinotti cells terminate on distal dendrites of pyramidal cells to influence the dendritic processing and integration of synaptic inputs .

By controlling activity-dependent GABA release, NRG1 might repress the activity of pyramidal neurons

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Erbin

Htra1

Htra2

Htra3

PSD-95

SAP97

PTP-BL

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PROTEINS OF THE POSTSYNAPTIC DENSITY

G. Banker 1, L. Churchill 1, and C. W. Cotman 1 1 From the Department of Psychobiology, University of California, Irvine, California 92664

The Postsynaptic Density Proteins Homer and Shank Form a Polymeric Network Structure Mariko Kato Hayashi1, 2, ,  , Chunyan Tang3, Chiara Verpelli4, Radhakrishnan Narayanan1, Marissa H. Stearns1, 6, Rui-Ming Xu5, 7, Huilin Li3, Carlo Sala4 and Yasunori Hayashi

www.cco.caltech.edu

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