Membrane compartments of the cell

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Membrane compartments of the cell

• Cytoskeleton

Svetlana Lutsenko, Dept. Biochemistry and Mol.
Bology MRB 624, Ext. 4-6953, lutsenko_at_ohsu.edu
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• Reading for the Cytoskeleton portion
• Alberts Essential Cell Biology pp.513-532

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Mechanisms by which molecules can pass through
membranes

• Transport of various molecules, including
  proteins, DNA and RNA through large protein-lined
  pores. Specificity of transport is based on size
  exclusion
• Simple diffusion and protein-mediated transport
  of ions and small molecular weight nutrients,
  such an amino-acids and sugars
• Vesicular transport is mediated by membranes that
  bud off as a vesicles from their original
  compartment and carry out specific cargo (ions,
  proteins, neurotransmitters) to another
  compartment

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Cellular Compartments and Their Functions

• Cytosol many biosynthetic pathway synthesis of
  cytosolic protein
• Nucleus DNA and RNA synthesis
• Mitochondria energy metabolism, urea cycle
• Endoplasmic Reticulum Protein Secretion
  Synthesis of Membrane Proteins
• Golgi Distribution and Modification of Secreted
  Proteins
• Lysosomes Degradation of proteins and other
  molecules
• Peroxisomes Degradation of Certain Fatty Acid

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Nucleus

• The nucleus is a membrane bound structure that
  contains the cell's hereditary information and
  controls the cell's growth and reproduction.
• It is commonly the most prominent organelle in
  the cell

http//biology.about.com/library/weekly/aa032300a.
htm
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Nuclear Membranes

• The nuclear content is located in the nuclear
  lumen and is surrounded by a double membrane or
  nuclear envelope, composed of inner membrane and
  outer membrane.
• The outer membrane is contiguous with the ER
• The nuclear membrane contains nuclear pores,
  which provide selective access into and out of
  the nuclear lumen
• The inner membrane has a protein lining called
  the nuclear lamina, which binds to chromatin and
  other nuclear components.

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The Nuclear Pore Complexes form a continuous
aqueous channel between cytoplasm nucleoplasm
nuclear pore complex is large about 120 million
Daltons

• -30 different proteins found in pore basic
  subunit repeated 16 times. Central granule" now
  called "transporter" functions to move molecules
  through pore. There is a ring of proteins that
  anchors pore to N.E. and the "basket" of fibers
  with unknown function
• no obvious motor proteins were found

Proposed mechanism -transport factors with cargo
destined to pass through nuclear pore bind to
pore increasing their local concentration.
Higher local concentration allows diffusion
across the diffusion barrier channel
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The Nucleolus

• The region of the nucleus where portions of
  chromosomes that contain genes coding for
  ribosomal RNA are transcribed and ribosomal
  subunits are assembled

• Stretch of DNA with rRNA genes nucleolar
  organizing region (NOR)
• Ribosomal proteins are synthesized in cytoplasm
  and transported into the nucleus
• These proteins self associate with appropriate
  rRNA during rRNA synthesis forming immature
  ribosomal subunits
• Ribosomes finish self assembly in cytoplasm

http//biology.about.com/library/weekly/aa032300a.
htm
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Endoplasmic Reticulum
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The Endoplasmin Reticulum (ER) is an extensive,
extra-nuclear membrane system with the following
functions

• ER is a home for various enzymes involved in
  protein folding , drug detoxification, membrane
  lipid biosynthesis, cholesterol and fatty acid
  metabolism
• ER is an entry point for protein sorting.
  Targeting of these proteins is mediated by signal
  sequence. The membrane proteins are inserted
  into the ER membrane in their proper
  orientation. Secreted proteins are translocated
  into ER lumen and then transported to the
  destination place

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Rough and Smooth ER

• Two regions of the ER differ in both structure
  and function. Rough ER has ribosomes attached to
  the cytoplasmic side of the membrane. Smooth ER
  lacks attached ribosomes. Typically, the smooth
  ER is a tubule network and the rough ER is a
  series of flattened sacs.

The smooth ER has a wide range of functions
including carbohydrate and lipid synthesis. It
serves as a transitional area for vesicles that
transport ER products to various destinations.
In liver cells the smooth ER produces enzymes
that help to detoxify certain compounds. In
muscles the smooth ER assists in the contraction
of muscle cells and in brain cells it synthesizes
male and female hormones.
http//esg-www.mit.edu8001/esgbio/cb/org/er.gif
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The rough ER manufactures membranes and secretory
proteins.

In leukocytes the rough ER produces antibodies.
In pancreatic cells the rough ER produces
insulin.

• The rough and smooth ER are usually
  interconnected and the proteins and membranes
  made by the rough ER move into the smooth ER to
  be transferred to other locations.

The cytoplasm has a reducing environment, while
ER lumen is oxidizing . This difference is
generated by unequal distribution of trypeptide
glutathione and is essential for formation of
disulfide bonds in proteins and for proper folding
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Mitochondria
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Mitochondria (singular mitochondrion) are the
sites of aerobic respiration, and generally are
the major energy production center in eukaryotes
The number of mitochondria range from one to
thousands per cells. They are often positioned
in cells nearest to sites of energy
utilization One of the richest sources of
mitochondria is a hummingbird flight muscle
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Mitochondria are a double membrane organelle in
which the inner membrane is in-folded to form
cristae.
The outer membrane is a fairly simple
phospholipid bilayer, containing porins, proteins
that render it permeable to molecules of about 10
kilodaltons or less. Ions, nutrient molecules,
ATP, ADP, etc. easily pass through the outer
membrane and enter the intermembrane space The
inner membrane is more complex and contains
respiratory chains and transporters
The matrix lies within the inner membrane. The
access to this compartment often requires
specific transporters
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Four possible localization for mitochondrial
enzymes
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The Golgi Complex
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Located near cell nucleus, consists of flattened,
membrane-bounded sacs (cisternae) forming a stack
Each stack has cis-face is an entry face -
adjacent to ER to accept incoming vesicles
trans-face is an exit face points towards
plasma membrane, produces vesicles for forward
flow
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The function of the Golgi is to transport and
process secreted and membrane proteins from ER to
the cell surface
Cisternae segregated into convex ("cis"), medial
(middle), and concave ("trans") compartments.

• Cis removal of mannose,
• phosphorylation
• Medial removal of mannose, addition of
  N-acetylglucosamine
• Trans Removal of galactose, addition of sialic
  acid
• TGN addition of sialic acid, Sorting

ER
cys
medial
trans
TGN
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Vesicular Transport
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The Endocytic Pathway

• Endosomes and Lysosomes

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• Lysosomes
• Lysosomes are active in recycling the cell's
  organic material and in the intracellular
  digestion of macromolecules.
• Lysosomes contain various hydrolytic enzymes that
  are capable of digesting nucleic acids,
  polysaccharides, fats and proteins.
• The inside of a lysosome is acidic.
• In humans, a variety of inherited conditions can
  affect lysosomes. These defects are called
  storage diseases and include Pompe's disease and
  Tay-Sachs disease. People with these disorders
  are missing one or more of the lysosomal
  hydrolytic enzymes.

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The Cytoskeleton
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Cytoskeleton is a network of protein filaments in
the cytoplasm

• Main functions
• Supports large volume of the cytoplasm
• Participates in large-scale movements associated
  with the changes in cell shape and cell motility
• Provides machinery for organelle transport,
  chromasome segregation during mitosis, and cell
  division

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Major components of cytoskeleton
Microtubules
Actin filaments
Intermediate filaments
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The cytoskeletal filaments

• Common Features
• Linear polymers of protein subunits
• Actin ( 8 nm in diameter)
• Intermediate Filaments ( 10 nm in diameter)
• Microtubules ( 24 nm in diameter)
• Filaments are dynamic, i.e. they can assemble and
  disassemble
• Highly conserved

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Intermediate Filaments

• Intermediate filaments enable cells to withstand
  mechanical stress when cells are stretched.
• They can span the entire cytoplasm and are
  anchored to the plasma membrane.

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The Microtubule Cytoskeleton

• Also penetrates the entire volume of the cell
• Whereas actin fibers are concentrated at the
  periphery, most microtubules radiate from a
  central location in the cell
• Main functions intracellular transport and
  mitosis

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Microtubules

• Microtubules provide an organizational
  structure in an interphase cell and separate
  chromosomes in a dividing cell

http//www.circs.neu.edu/external/Frank.Gibbons/sp
indle.html
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Microtubules Provide Tracks for Transport
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• Microtubules are long hollow cylinders made of
  tubulin

• Protofilaments are linear chains of tubulin
  dimers, a parallel bundle of 13 protofilaments
  forms a microtubule
• There are three kinds of tubulins, each with many
  subtypes
• a-tubulin and b-tubulin form a/b tubulin dimers
  and represent the basic building block of
  microtubules
• g-tubulin is involved in more specialized
  processes, such as nucleation
• Microtubules have a GTP cap stabilizing the
  ends.

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Motor Proteins

• Motor proteins bind to microtubules and move by
  cycles of conformational changes using energy
  from ATP.
• One end of the protein can bind to specific
  cellular components.

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Actin filaments microfilaments

• Actin is the most common protein in the cytoplasm
• Actin filaments are concentrated beneath the
  plasma membrane and give the cell mechanical
  strength
• Assembly of actin filaments can determine cell
  shape and cause cell movement
• Association of actin filaments with myosin can
  form contractile structures

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• Spectrin
• Principal component of the cytoskelton (protein
  meshwork underlying surface of the red cell)
• Maintains structural integrity of the red cell
  (e.g. biconvave shape)
• Long thin flexible rod
• Necessary as red cells go through small
  capillaries