Membranes: Keeping things where they belong

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Membranes Keeping things where they belong

• Separate functional and anatomic fluid
  compartments in the body.
• Regulate the transport of materials between
  compartments

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Connections between plasma membranes

• Extracellular matrix primarily secreted by
  fibroblasts.
• Collagen forms cable-like fibers that provide
  tensile strength especially important in skin
  and blood vessels.
• Scurvy in vitamin C deficiency these fibers are
  not properly formed.
• Elastin rubber-like protein where elasticity
  (ability to return to pre-stress orientation) is
  important especially important in arteries and
  lungs.
• Fibronectin promotes cell-cell adhesion and can
  hold cells in position.

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Adjacent intestinal epithelial cells
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Tight Junctions
Intracellular
Extracellular
Transmembrane Proteins
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Connections between plasma membranes

• Extracellular matrix

• Tight junctions zona occludens
• Impermeable (usually) connectio
• ns between cells.
• Cell membranes are attached to each other by
  strands of junctional proteins.

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Extracellular
Intracellular keratin filaments
Intracellular
Spot Desmosome
Thickened plaque area
Intercellular filaments (commonly glycoproteins)
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Connections between plasma membranes

• Extracellular matrix
• Tight junctions zona occludens

• Spot desmosomes macula adherens (20 nm)
• anchor cells together with some space to
  accommodate movement/stretching.
• Cytoplasmic plaque
• Intracellular intermediate filaments through
  cells connecting various plaques
• Intercellular glycoprotiens connect the cells

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Extracellular
Intracellular
Passage of ions And small molecules
1.5 nm
Large molecules blocked
Gap Junctions
Connexons
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Connections between plasma membranes

• Extracellular matrix
• Tight junctions Tight junctions zona occludens
• Spot desmosomes macula adherens

• Gap Junctions no fancy latin name 2-4 nm
• Communication between cells through connexons
• Permit passage of small ions and particles
  between cell's cytoplasm

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Membrane Transport

• Passive movement of material without the
  expenditure of energy.
• Simple Diffusion
• particles in random motion display net movement
  relative to two conditions
• Chemical gradient material moves "down" it's
  concentration gradient.

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Membrane Transport

• Passive movement of material without the
  expenditure of energy.
• Simple Diffusion
• particles in random motion display net movement
  relative to two conditions
• Chemical gradient material moves "down" it's
  concentration gradient.

• Osmosis the movement of water "down" it's
  concentration gradient.
• Osmotic pressure a "negative" effective
  pressure that acts to "pull" water

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Semi-permeable
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X mmHg
X mmHg
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Membrane Transport

• Passive movement of material without the
  expenditure of energy.
• Simple Diffusion
• particles in random motion display net movement
  relative to two driving force conditions
• Chemical gradient material moves "down" it's
  concentration gradient.
• Ionic charge electrical attaction/repulsion

• Other factors influencing volume-rate diffusion
• Permeability of the membrane to the substance
• Lipid-soluble-passes through
• Water-soluble - generally require selective
  channels or pores
• Molecular weight of the substance
• Surface area
• Distance (thickness of the membrane)
• Facilitated (carrier-mediated) diffusion - the
  diffusion of the material occurs via specialized
  protein "carriers"

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Membrane Transport

• Passive movement of material without the
  expenditure of energy.
• Simple diffusion

• Facilitated (carrier-mediated) diffusion - the
  diffusion of the material occurs via specialized
  protein "carriers"
• particles in random motion display net movement
  relative to their electrochemical gradient
• Display unique characteristics
• Specificity only one molecule (or class of
  molecules) transported
• Saturation The rate of transport of molecules is
  limited to the number of carriers.
• There are only so many lifeboats on the Titanic
• Competition When the carrier can transport
  multiple forms of a molecule (or drugs that
  closely resemble the molecule), the multiple
  forms compete for the limited number of carriers.
  
• If a ferry has 100 seats, and 70 are occupied by
  women, ony 30 men are getting across.

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Membrane Transport

• Passive movement of material without the
  expenditure of energy.
• Simple diffusion
• Facilitated (carrier-mediated) diffusion

• Active Transport requiring the expenditure of
  energy
• Primary Energy used directly in transport of
  the molecule(s)

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Membrane Transport

• Passive movement of material without the
  expenditure of energy.
• Simple diffusion
• Facilitated (carrier-mediated) diffusion
• Active Transport requiring the expenditure of
  energy
• Primary Energy used directly in transport of
  the molecule(s)

• Typical series of events
• ATP is used to phosphorylate the carrier
• carrier becomes exposed to the side with low
  concentration of the molecule to be transported
• Increased affinity for the transported molecule
• Binding of the molecule usually causes
  conformational (structrural) change
• Molecule is exposed to high concentration side
• Carrier is dephosphorylated
• Affinity for the molecule decreases, and the
  molecule is released
• Simple design one molecule (or class), one
  direction
• Complex designs multiple molecules mutiple
  directions

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Membrane Transport

• Passive movement of material without the
  expenditure of energy.
• Simple diffusion
• Facilitated (carrier-mediated) diffusion
• Active Transport requiring the expenditure of
  energy
• Primary Energy used directly in transport of
  the molecule(s)
• Typical series of events
• ATP is used to phosphorylate the carrier
• carrier becomes exposed to the side with low
  concentration of the molecule to be transported
• Increased affinity for the transported molecule
• Binding of the molecule usually causes
  conformational (structrural) change
• Molecule is exposed to high concentration side
• Carrier is dephosphorylated
• Affinity for the molecule decreases, and the
  molecule is released
• Simple design one molecule (or class), one
  direction
• Complex designs multiple molecules mutiple
  directions

• Counter-transport multiple molecules, opposite
  direction (3Na/2K)
• Co-transport multiple molecules, same direction
  (not common)
• Secondary Potential energy of another molecule
  used (commonly Na)

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Membrane Transport

• Passive movement of material without the
  expenditure of energy.
• Simple diffusion
• Facilitated (carrier-mediated) diffusion
• Active Transport requiring the expenditure of
  energy
• Primary Energy used directly in transport of
  the molecule(s)
• Secondary Potential energy of another molecule
  used (commonly Na)

• Counter-transport multiple molecules, opposite
  direction (Na/H)
• Co-transport multiple molecules, same direction
  (Na/Glucose)
• Vesicular
• Clathrin "coated pit" pathway
• Endocytosis
• Exocytosis
• Potocytosis- the caveolae pathway
• Specialized caveolin-rich "pit" in membranes with
  cholesterol-stabilized constituents
• Sometimes maintains "tether" connection to the
  membrane
• Involved in many receptor-mediated communication
  processes

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Membrane Potential
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Membrane Potential

• An electrical potential caused by unbalanced
  distribution (in/out) of cations and anions.
• All cells
• Can primarily be attriubuted to
• Na/K exchange pump pumps more cations out than
  anions in.
• Differences in permeability to Na and K cell is
  much more permeable to K than to Na the
  concentration gradient (K our) is balanced by the
  attraction of anions inside.
• Membrane impermeable anionic proteins

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Membrane Potential

• An electrical potential caused by unbalanced
  distribution (in/out) of cations and anions.
• All cells
• Can primarily be attriubuted to
• Na/K exchange pump pumps more cations out than
  anions in.
• Differences in permeability to Na and K cell is
  much more permeable to K than to Na the
  concentration gradient (K our) is balanced by the
  attraction of anions inside.
• Membrane impermeable anionic proteins

• Uses of the membrane potential
• Communication via electrical transmission -
  primarily nerve and muscle
• Secondary energy source for transport

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Cellular Communicaton
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Autocrine
Endocrine
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Neural
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Communications Ligand-receptor mediation

• Gated Channels- receptor activation "opens"
  channels for ions to move
• Electrical potential transmission
• Ions controlling secretion (eg Ca)
• Second-messenger systems
• G-protein coupled

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E1
?
E2
ß
a
GDP
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E1
E2
a
a
GDP
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Communications Ligand-receptor mediation

• Gated Channels- receptor activation "opens"
  channels for ions to move
• Electrical potential transmission
• Ions controlling secretion (eg Ca)
• Second-messenger systems
• G-protein coupled

• General Scheme
• Inactive alpha,beta, and gamma subunits
  together GDP bound
• Binding of GTP to alpha subunit activates alpha
  /- betagamma subunits alter activity of an
  effector molecule (kinase or phsphatase)
• Hydrolysis of GTP to GDP inactivates the G
  protein subunits
• Inactivation of G-protein does not necessarily
  inactivate effector. Thus, the chemical half-life
  and biological half-life are often very
  different.
• The same second messenger can cause different
  responses in different cells

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epinephrine
Adenylyl Cyclase
Beta-adrenergic receptor
?
ß
as
as
adenosine
GDP
ADP
PKA
Phosphorylate specific protein
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Communications Ligand-receptor mediation

• Gated Channels- receptor activation "opens"
  channels for ions to move
• Electrical potential transmission
• Ions controlling secretion (eg Ca)
• Second-messenger systems
• G-protein coupled

• General Scheme
• Examples
• Adenylyl Cyclase
• Gs-alpha stimulates AC to enzymatically form
  cyclic-AMP from ATP
• cAMP activates protein kinase A, which in turn,
  phosphosylates a target protein
• Degradation of cAMP to AMP may overwhelm th
  ability to re-phosphorylate adenosine is
  produced
• Adenosine activates an inhibitory G-protein which
  inhibits AC- negative feedback control

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?
PIP2
PKC
ß
as
as
DAG
Phosphorylate specific protein
IP3
Signals the release of Calcium from ER
Ca
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Communications Ligand-receptor mediation

• Gated Channels- receptor activation "opens"
  channels for ions to move
• Electrical potential transmission
• Ions controlling secretion (eg Ca)
• Second-messenger systems
• G-protein coupled
• General Scheme
• Examples
• Adenylyl Cyclase
• Gs-alpha stimulates AC to enzymatically form
  cyclic-AMP from ATP
• cAMP activates protein kinase A, which in turn,
  phosphosylates a target protein
• Degradation of cAMP to AMP may overwhelm th
  ability to re-phosphorylate adenosine is
  produced
• Adenosine activates an inhibitory G-protein which
  inhibits AC- negative feedback control

• Phosphatidylinositol isphosphate (PIP2)
• Gs-alpha activates phospholipase C (PLC)
• PLC cleaves PIP2 inot inositol-triphosphate (IP3)
  and diacylglycerol (DAG)
• IP3 causes the release of intracelular Ca
• ?Calmodulin is activated by binding with Ca
• ?Activated calmodulin then activates or
  inhibits other proteins
• DAG acts as a separate second messenger (often
  protein kinase C PKC).

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Apoptosis
Direct hydrolysis
Activation of other systems
Caspases
OH-
?
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Cell DeathEnd of the road

• Necrosis usually associated with ischemia or
  abrupt damage
• Disorganized loss of membrane integrity
• Cell swelling and rupture lysosomal enzymes
  released
• Inflammatory response
• Apoptosis ordered death
• Activation of Caspases by
• mitochondrial cytochrome release
• second messenger system
• transcriptional regulation
• Caspases activate other caspases and addtional
  hydrolytic enzyme systems cleave cellular
  components into organized fragments for disposal