Transcript Intro Membranes WRLa..

Membranes: Keeping things where they belong
• Separate functional and anatomic fluid compartments in the
body.
• Regulate the transport of materials between compartments
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 prestress orientation) is important; especially important in arteries and
lungs.
– Fibronectin: promotes cell-cell adhesion and can hold cells in position.
Adjacent intestinal
epithelial cells
Tight Junctions
Intracellular
Extracellular
Transmembrane Proteins
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.
Extracellular
Intracellular keratin
filaments
Intracellular
Spot
Desmosome
Thickened
“plaque” area
Intercellular filaments
(commonly glycoproteins)
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
Extracellular
Intracellular
Passage of ions
And small molecules
1.5 nm
Large molecules
blocked
Gap Junctions
Connexons
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
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.
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
Semi-permeable
X mmHg
X mmHg
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"
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.
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)
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
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+)
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
Membrane Potential
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
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
Cellular Communicaton
Autocrine
Endocrine
Neural
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
E1
E2
GDP
GTP
E1
E2
GDP
GTP
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 +/- beta:gamma 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
epinephrine
Adenylyl Cyclase
Beta-adrenergic
receptor
AC
adenosine
GTP
ATP
cAMP
GDP
ADP
PKA
Phosphorylate specific protein
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
PIP2
PLC
PKC
DAG
IP3
Signals the release of
Calcium from ER
Ca++
Phosphorylate
specific protein
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]).
Apoptosis
Direct hydrolysis
Activation of other systems
OH
-
Caspases
?
Cell Death
End 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