Psy 111 Basic concepts in Biopsychology

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• Psy 111 Basic concepts in Biopsychology
• Lecture 2 Cells and their Proteins

Website http//mentor.lscf.ucsb.edu/course/fall/p
syc111/
Office Hours M 1000 am Noon Psych 2821
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Lecture Objectives

• Describe the major functions of the cells of the
  nervous system neurons and glia.
• Describe the different parts of a neuron and
  define the concept of compartmentalization.
• Describe the structure and role of the cellular
  membrane and cytoskeleton.
• Identify the basic functions of mitochrondira,
  the nucleus, endoplasmic reticulum, and Golgi
  apparatus.
• Describe the dogma of gene expression and the
  protein synthesis machinery common to all cells.
• Describe transcription and the mechanisms of
  its regulation with emphasis of the importance of
  chromatin remodelling.
• Describe translation and the mechanisms of its
  regulation and discuss RNA silencing.
• Describe post-translational processing and where
  it occurs.
• Describe protein transport within the neuron.

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Levels of Analyses

• We can try to understand brain function and its
  relation to psychological processes at multiple
  levels.
• We can analyze behavior,
• activity in specific parts of the brain,
• the connections between these parts of the brain
  (systems),
• the relations between cells with individual parts
  of the brain,
• the activity of individual cells (e.g. neurons),
• the connections between cells (e.g. synapses),
• to the activity of individual molecules.

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Cellular Components of the Nervous System

• Cells of the nervous system
• Parts of a cell
• Protein synthesis a.k.a. gene expression

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Cells of the Nervous system

• Nervous system (brain, spinal cord, and nerves)
  is made up of 100s of billions of cells (neurons
  and glia).

• Only 10 (100 billion) of cells in the brain are
  neurons
• the rest of the brain is non-neuronal!

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Cells of the Nervous System
I. Neurons cells that are capable of sending
and receiving chemical signals. - and are
specialized to transmit information from place to
place with electrical signals.
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Types of Neurons
Classification on Type of Connections Class
- afferent/sensory - efferent/motor
-interneuron
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Types of Neurons

• Neurons differ in
• Location in nervous system.
• Morphology
• Multipolar-motor neurons projection neurons in
  brain
• Unipolar-sensory neurons
• Bipolar-sensory neurons
• Interneurons-in spinal cord and brain
• Polarity refers to the number of processes
  (out-growths) coming from the cell body (refers
  to dendrites and axon)
• Chemicals used to communicate.

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Morphology number or length of processes
Local (Golgi Type II)
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Types of Neurons
Classification on Neurotransmitters -Chemical
amino acids, monamines, peptides, etc
co-localization -Function inhibitory,
excitatory, modulatory
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Cells of the Nervous System II

• Glial cells
• Latin for glue
• make up 90 of your brain
• we now know that they are more than structural
  support!!!!
• Myelin producing glia enhance electrical
  signaling (come back to this later)
• Oligodendrocytes (CNS brain spinal cord)
• Schwann cells (PNS rest of our nervous system)
• Astrocytes largest glia, star-shaped
• Regulate nutrients and waste for neurons
• involved in response to injury
• Remove and release ions (charged molecules)
  neurotransmitters
• Microglia involved in response to injury or
  disease, remove debris, form scars

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Astrocytes
Neurons
Blood vessel
Brain tissue stained for an astrocyte marker
(Glial Fibrial Acidic Protein - only found in
astrocytes)
Astrocytes
-star-shaped cells -assist in the transfer of
chemicals (nutrients and waste products) from the
blood to the nervous system wrap around blood
vessels -also take up and release ions,
neurotransmitters. ?may be key players in
neurotransmission.
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Cellular Components of the Nervous System

• Cells of the nervous system
• Parts of a cell
• Protein synthesis a.k.a. gene expression

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Parts of the Neuron compartmentalization
functional segregation.
Dendrites input Body protein
production Initial Segment integration Axon
conduction Terminal output
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Microstructure of Soma/Cell Body
-compartmentalization -specialization of cellular
components
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Cell (or Plasma) Membrane
Cells live in an aqueous (water-based)
environment but require ability to maintain
internal state in a specific state. This
requires a barrier to outside of cell which is
achieved by the cell membrane -gt defines intra-
vs. extra-cellular spaces.
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Cellular membrane
Phospholipid bilayer.
Hydophillic-interacts with water/environment
Hydophobic -barrier to water.
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Cellular membrane
Proteins receptors channels
pumps enzymes
Note proteins are the functional units of
biology every action is carried out by a
protein/enzyme

• Membrane plays a critical role in communication
  between cells.
• An important aspect of the membrane is that it is
  dynamic protein components change and move
  around critical for neuroadaptations.

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Cytoplasm
Aqueous solution (cytosol) Organelles
Cytoplasm comprises the area between the plasma
membrane and the nucleus which includes cytosol
(aqueous environment) and cellular organelles.
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Cytoskeleton
Protein scaffolding -allows localization and
interconnection between organelles. -give shape
to neurons or glia dynamically modulated ? role
in the plasticity of neurons.
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Mitochondria cells power house.
Cellular Energy
Structure Rod- or oval-shaped body surrounded by
two membranes. Inner membrane folds into matrix
of the mitochondrion, forming cristae. Functions
Major site of ATP production, O2 utilization, and
CO2 formation. Contains enzymes of Krebs cycle
and oxidative phosphorylation.
Double membranes contains metabolic
proteins Metabolic enzymes provide usable
energy for cell
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Nucleus
Nuclear Envelope separates from
soma Chromosomes store genetic info
(DNA) Nucleolus production of RNA
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Endoplasmic Reticulum Rough vs.
Smooth
Membranes Enzymes Ca store
Membranes Ribosomes (enzyme complex)
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Golgi Apparatus
Membranes Enzymes
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Basic Cellular Components of the Nervous System

• Cells of the nervous system
• Parts of a cell
• Protein synthesis a.k.a. gene expression

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Compartmentalization
Dendrites input Body protein
production Initial Segment integration Axon
conduction Terminal output
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Protein Synthesis Cell Differentiation/Specializ
ation

• All cells of an organism are initially derived
  from a single cell and thus share the same genes
  (DNA).
• But cell can perform different biological
  function through selective expression of DNA/
  synthesis of protein
• i.e. a neuron is a neuron because it makes a
  specific set of proteins

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Gene Expression Protein Synthesis
Gene Expresion DNA mRNA Protein
The end result of gene expression is a specific
protein that contributes to the function of the
cell.
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Transcription
DNA -gt mRNA
-only sense or template DNA is transcribed to
RNA. -RNA is complementary to template DNA
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Allows Exons -Multiple versions of same gene.
-Multiple products to be co-transcribed.
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-end result of some forms of neuronal
communication, hormone actions, target of drug
action
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Epigenetics/Chromatin Remodeling DNA Methylation
Addition of methyl groups to nucleotides of DNA
(at CpG) will reduce transcription of the gene.
This type of change is typically permanent due to
maintenance enzymes (e.g. Dnmt1) and initially
thought to only occur in the development but
recently it has been shown to be produced by drug
exposure
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Epigenetics/Chromatin Remodeling Histone
modifications
?Acetylation ?Methylation ?Trascription
?Acetylation ?Methylation ?Trascription
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EpigeneticsChromatin Remodeling Histone
Modifications

• Addition of acetyl groups to histones will
  facilitate transcription of the gene.
• Histone Acetyltransferase (HAT) adds acetyl group
  to histone.
• Histone deacetylase (HDAC) removes acetyl group.
• Addition (HMT) or removal (HDM) of methyl groups
  to specific histones also modulates
  transcription.
• These enzymes are modulated by neurotransmission
  (or drugs).

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Protein Synthesis Cell Differentiation/Specializ
ation

• All cells of an organism are initially derived
  from a single cell and thus share the same genes
  (DNA).
• But cell can perform different biological
  function through selective protein expression
• Much of the cell-type specific gene expression is
  controlled by epigenetic mechanisms.

But back to our mRNA
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mRNA Transported to Cyoplasm
Specialized chaperone proteins serve to bring
mRNA out of nucleus to the cytoplasm ensure
other molecules do not enter or exit nucleus.
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Translation on Ribosomes
mRNA -gt polypeptide
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Translation on Ribosomes
Free ribosome
rER ribosome
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rER versus Free Ribosomes
rER -gt encapsulated proteins proteins
destined to be membrane-bound proteins destined
to be secreteted
Free ribosomes Cytoplasmic proteins Nuclear,
mitochondrial, or perisomal proteins
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Coding of Genetic Information Codons
Condon functional unit of DNA (RNA) code 3
nucleotides
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• Classes of amino acids
• Have different properties
• Contribute to overall properties of protein

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Peptide Bonds
Proteins (or polypeptides) are comprised of 2 -
1000s of amino acids joined together via a
common method
Each linage between amino acids is formed by a
peptide bond in a sequential fashion -ribosome
is specialized enzyme complex for making peptide
bonds between aas with the sequence of aas
determined by mRNA. -gtProduct of ribosome is a
poly-peptide pre-protein.
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Blocking TranslationRNA Silencing/Interference

• RNA silencing/interference a short strand of RNA
  can bind to a complimentary segment of the mRNA
  to block translation.
• The inhibiting strand is referred to as
  micro-RNA (miRNA) if it is endogenously
  produced.
• The inhibiting strand is referred to as short
  hairpin loop-RNA (shRNA) if it is artificially
  produced potential therapeutic.

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Post-translational Processing
Golgi Apparatus Cleavage into smaller
polypeptides
N.B. this should refer to polypeptides because
only end functional product is a protein.
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Post-translational Processing
Golgi Apparatus can Glycosylation addition
of sugars (carbohydrates). Phospholipidation
addition of fats.
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Site of Translation and Modifications
Translation on rER (or free ER)
Modification and packaging into vesicle
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Protein Transport
1. Axoplasmic Flow -slow -movement of cytoplasm
in axon 2. Anterograde Axonal Transport -fast -en
ergy dependent -kinesin microtubules 3.
Reterograde Axonal Transport -fast -energy
dependent -dynein microtubules
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Post-translational Processing
Once the final polypeptide is derived needs to
take on proper conformation or shape may
involve multiple polypeptides working together.
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Protein Complexes and Incorporation
Receptors
Vesicle
Channels
Scaffolding proteins
Cytoskeleton
Networks of scaffolding proteins coordinate many
types of proteins -e.g. Postsynatpic density
critical to proper neuronal communication.
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Summary of Protein Synthesis
1. Transcription
2. Translation

• Post-translational processing trafficking

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Compartmentalization
Dendrites input Body protein
production Initial Segment integration Axon
conduction Terminal output
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