How do cells Communicate...    in multi-cell organisms cell-to-cell contact is critical. 
            - cell membranes contain specific protein-receptors, which bind & transmit
extra-cellular signal molecules converting signals into specific cellular response
   Some UNIVERSAL PRINCIPLES of cell communication are now well known

cells may use many different signal molecules,
                but only a few mechanisms have survived throughout evolution.
                        an analogy: auto industry...    cars basically have same parts (engines, fenders, lights)
                                                          but the variety of different patterns is boundless.

                         here an exogenous molecule is received by a cell,
                             & converted (transduced) into a response by the receiving cell.

        pattern is remarkably similar in all cells;  probably evolved very early, 
                             even before first multi-cellular cells (maybe in single cell prokaryote);
                             and has been highly conserved in today's ancestral cells.

                                         Concept Activity - Chapter 11.1 -  How do Cells Communicate with Each Other
                           Concept Activity - Chapter 11.1 -
Overview of Cell Signaling








   mating in yeast cells*         (picture of yeast)
                sex-1    ["a"-cell : releases a-factor (peptide of 12 aa's) - binds to sex-2 receptors]
                sex-2   ["
a"-cell : releases a-factor - binds to sex-1 receptors]
                                            results = is fusion of 2 cells (mating) producing diploid cell.

   Signaling can be LOCAL or DISTANT...   examples*    

           PARACRINE (local) SIGNALING
            local regulator chemical messengers are targeted to specific receptors 
            often includes: growth factor proteins that promote cell division & growth
                                  & neurotransmitters that move across synapses to other neurons
            specialized cells release molecules (often hormones) into blood vessels of
            circulatory system,  hormones move to distant target cells... elicit response









    Communication via CELL-TO-CELL CONTACT - here the signaling is direct:


                  gap junctions & plasmodesma...
                          results in cytoplasmic continuity favoring cellular interactions...
                                          fig 11.3a*


                  cell surface contacts... 
                          receptor protein specificity
(as above with yeast cells)...
                                          fig 11.3b*









 Communication via CELL SIGNALING...
         The 3 Stages of Cell Signaling Process...

                              or the  Properties of a Signal Transduction Pathway... 

            RECEPTION,   TRANSDUCTION,  and  RESPONSE      
    1.  Reception...  is not unlike recognition of enzyme for its substrate [ES complex]
                ... akin to the lock-&-key hypothesis of enzyme-substrate recognition (Km & Vmax)
                ... ligand molecules (usually water soluble) are recognized by
                                  only one receptor protein bound within a cell membrane
   2.  Transduction... 
leads to a conformation change in receptor
                ... shape change results in receptor interacting with other intra-cellular molecules
                ... may result in multiple, conformational/structural changes in other cellular proteins

inactive enzymes ---> active enzymes, & so on, etc...         fig 11.6*
    3.  Response...  usually a cellular activity, as enzyme catalysis, or
                            the rearrangement of cytoskeleton (movement), or specific gene activity.

                                          Concept Activity - Chapter 11.2 - Reception
Chapter 11.4 - Cellular Responses













 an Example of a Receptor Protein & Signal Transduction System

 1.  G-Protein Receptors...  receptor proteins that bind GTP/GDP    
                                                                          & convert between active & inactive forms


       G-protein receptor structure... has 7 transmembrane
                & has site site for receptor molecule and G-protein to bind      fig 11.7*


       a signal molecule binds to a receptor --> conformation change -->   
               an inactive G-(GDP)-protein now binds GTP (replacing GDP)...    fig 11.7a*  
               and active G-(GTP)-protein stimulates other inactive enzymes.   fig 11.7b*
       G-Protein has its GTP hydrolyzed   -->   inactivates G-protein           fig 11.7c*
               cholera and botulin toxins... bind to G-protein keeping it active -->

       A specific example of G-protein cellular responses:
                Fight of Flight Response...  (see fig 11.11
* & figure*
net result...   1 signal molecule gives multiple-enhanced response.
                                                           Concept Activity - Chapter 11.4 -  Signal-Transduction Pathways
                                                                                                                               -  Build a Signaling pathway 







 The specificity of cell signaling is varied among cells
                                           and leads to a multiplicity of

     Other example of signal transduction mechanisms:

     1.  Gene activation by a growth factor                                 -  Campbell 8e-
figure 11.14

     2. Steroid hormone reception & myosin protein synthesis  -  Campbell 8e - figure 11.8

     3. Ligand gated ion channel signaling                                    -  Campbell 8e - figure 11.7*

     4. IP3-DAG and Ca signaling                                                 - Campbell 8e - figure 11.13*

             all of these signaling mechanism model themselves after the basic
             signal transduction mechanism. example.

    BACK       end cell communication










 you are not responsible for the material that follows below:

  other examples of Receptor Proteins & Signal Transduction Systems...

2. Tyrosine Kinase receptors...  receptor proteins that have kinase activity...
            i.e., they can add a
-PO4 group to tyrosine residues of inactive proteins 
                  making them active   --->   cell response                               fig 11.8*
         many growth factors (stimulate cell division & growth) function via tyr-kinases 

      ...  binding of growth factor (signal ligand) causes 2 single tyr-kinases to aggregate
     ...  the tyr-dimers, now each phosphorylate the others tyr residues via ATP kinase activity
     ...  the activated-phosphorylated dimer binds relay proteins, activating them,
                    which in turn (by cascade effect) can active up to 10 others, etc...

               net result... 1 signal molecule can trigger many proteins and multiple pathways.










more examples of Receptor Proteins & Signal Transduction Systems...

  3.  Ion channel Receptors...  [ligand gated protein channels]
              a protein
PORE in a membrane opens in response to binding a signal molecule
ex: a neurotransmitter as acetylcholine (Ach) opens channel and lets Na+ ions 
                     flood into cell, changing that cell's electrical charge (potential)
see fig 11.9*

                              How Potassium ion Channel works - 2003 Nobel Prize in Chemistry   H2O
   4.  Non-membrane bound [cytoplasmic - intracellular] Receptors...
             signal molecules diffuse through membrane, where binding to an 
intracellular receptor protein initiates a cellular response.
                                               ex:  steroid hormones  (see fig 11.10*)

          back to outlines                                                      a paradigmkey concepts*

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copyright c2007, Charles Mallery, Department of Biology, University of Miami, Coral Gables, FL 33124
                       Last Update - July 18, 2008







  the material below is not required reading.


  Review of Some Important Points of SIGNAL TRANSDUCTION PATHWAYS

        most are like dominos... one activates another, then another, then another...
                                    producing a significant cascade multiplication effect.

1.    an Enzyme Cascade* - a model phosphorylation cascade effect...
              enzyme activation is by protein phosphorylation by protein kinase enzymes,
              that transfer P from ATP to another enzyme protein, thereby activating it.

2.     2nd messenger signal molecules...        cyclic-AMP           [cAMP = see fig 11.11*]
              signal molecule (hormone epinepherine) leads to activation
                    of membrane bound inactive enzyme Adenyl Cyclase
                                 ATP   --- active adenyl cyclase--->   cyclic-AMP  
                    ( cAMP is inactivated by phosphodiesterase ).

              G-proteincAMP activation of protein-kinase-A                  see fig 11.12*
                             PKA, itself a kinase, can activate other proteins, etc...
                                (see epinepherine & glycogen breakdown -    see fig 11.15*








some more POINTS of cell communication via signal transduction:

3.  cholera  toxin 
        Vibrio cholerae grow in fecal infected waters, infect small intestine,
        produce toxin, which binds to a G-protein, prevents conversion of GTP --> GDP,
        thus G-protein remains active, causing cAMP to remain active....
                net result: small intestine secretes water and salts = perfuse diarrhea = fatal.

4.  Ca ions
       cells maintain a low cytoplasmic [Ca] by active transport of Ca out of cytoplasm
       pumps keep a low cytoplasmic [Ca], but high ER cisternae & mitoplasm [Ca]
  see fig 11.14*

               Ca itself functions as a 2nd messenger, like cAMP,
                       as [Ca] in cytoplasm goes up, activates Ca+ pumps, & other responses ensue...
                                 as muscle contractions, neurotransmitter release, etc...

5.   plant phytochrome action via G protein & Ca channels = greening*
        plant pigment involved in responses to light - seed germination, photoperiodism, flowering, etc... 








6.  gene activation via cascading signal transduction.            see fig 11.17*















5.   Other 2nd messengers and Ca activation...
                Diacylglycerol (DAG)   and   Inositol Triphosphate (IP 3)

        a.  signal molecule binds to a G-protein or a tyrosine-kinase receptor
        b.  G-protein  activates  phospholipase-C,   an enzyme that splits lipids
        c.  phospholipase-C splits the phospholipid, PIP 2, into   DAG  &  IP 3
        d.  IP 3, as a ligand, binds to Ca ion channel of ER and increases cytosol [Ca]
       e.  increased Ca binds to enzyme calmodulin, changes its conformation, which
        f.  activates additional kinases and/or phosphatases
   see figure *



















           Some specific examples of G-protein cellular responses:
                mouse embryos lacking one G-protein... show no blood vessel development
                some human embryos w/o  G-proteins... decreased senses (esp: vision & smell)
                cholera and botulin toxins... function by interfering w G-proteins.