Chapter 11 – Cell Communication

Forms of communication among cells:

-Direct contact between neighboring cells à cell junctions or cell surface interactions
OR
-No direct contact à distance signaling:
Increasing distance

1) Synaptic – very small (microscopic) diffusion distance of a signal/ligand (called a

between signaling
cell & target cell

neurotransmitter)

2) Paracrine – short diffusion distance of signal/ligand (called a hormone)

3) Endocrine – long diffusion distance of signal/ligand (called a hormone)

Signaling Stages:
1) Reception – ligand (released from the signaling cell) binds to receptor (only on the
target cells)

2) Transduction – internalization & conveyance/transmittance of signal from receptor to

target molecule

3) Response – action by target cell

Reception:
-Binding of signal/ligand molecule(s) to a receptor that results in the receptor’s activation

Receptor Types: (http://hurleybio210a.com/Site/Resource_Links_files/CellSignaling-ReceptorTypes.mov)

1) Transmembrane receptors – span the entire length of the plasma membrane;
anatomy/parts = ECD, TMD, ICD; used by extracellular signals/ligands (non-steroidal,
hydrophilic); 3 kinds:
i) G-protein-coupled receptors – ligand binding activates a G protein (promotes
exchange of GDP (inactive) for GTP (active)
ii) receptor tyrosine kinases – ligand binding causes dimerization of two subunits
iii) ion channel receptors – ligand binding causes channel protein to open,
allowing ions to cross

2) Intracellular receptors – not in the plasma membrane (usually in cytoplasm or

nucleus); used by steroid-based ligands (hydrophobic) that can diffuse directly across the
cell membrane to reach the receptor inside the cell

Transduction: (http://hurleybio210a.com/Site/Resource_Links_files/CellSignaling-Transduction.mov)
- Once a receptor is activated, it starts a cascade (domino effect) – pathway where one
interaction leads to another in turn leading to another and then another, and another, etc.
- Cascade pathways are usually regulated by phosphorylation (addition of phosphate
group by enzymes called kinases) and dephosphorylation (removal of phosphate group by
enzymes called phosphatases) events
- Pathways often rely on use of second messengers (small, non-protein molecules or ions;
e.g. cAMP, Ca++, IP3)
- Allows for amplification of initial signal
(http://highered.mheducation.com/sites/0072437316/student_view0/chapter7/animations.html#)
Cellular Response: (http://hurleybio210a.com/Site/Resource_Links_files/CellSignaling-CellularResponse.mov)
- What it is that a target cell does as a result of receiving the initial signal
- Examples include: proliferation (increased cellular division), metabolic regulation,
migration, transcriptional regulation (turning genes on or off), propagation of electrical
impulses, cellular shape change, initiation of immune responses, cell survival, or
programmed cell death (apoptosis)

Control & Attenuation (Fine-tuning) of Cell Responses:

1) Signal amplification – as little as one ligand molecule can result in the activation of
hundreds of thousands to millions of molecules inside the cell in order to generate a
response
2) Specificity of cell signaling – context of what proteins are present helps to determine
the response; different target cells may respond differently to the same signal/ligand
depending on what collection of relay proteins they possess
3) Signaling efficiency – use of scaffold proteins help to activate multiple relay proteins
simultaneously (rather than one at a time)
4) Termination of signal – cell responses need to be finite (eventually brought to an end);
done in several ways:
i) uncoupling of signal/ligand from receptor – although the affinity of a ligand for
a particular receptor might be high, the ligand does not remain bound forever
(once the ligand uncouples, the receptor inactivates and the signaling pathway
shuts down)
ii) cross-talk with reception of another signal/ligand – activation of a second
receptor on the same target cell can lead to a transduction pathway that shuts
down/cancels out the first pathway (caused by activation of the first receptor)
iii) internalization & ubiquitination of a receptor – immediately after reception
and initiation of transduction, some receptors are endocytosed and ubiquitinated
(marked for degradation via proteasome)

Apoptosis:
- Form of programmed cell death (“cellular suicide”) that may be initiated by some
signaling pathways in certain cells; it is not to be confused with necrosis (death caused by
accidental trauma that usually compromises the integrity of the cell membrane leading to
an inflammatory response)
- Death (or survival) signaling pathways can lead (or not lead) to activation of proteases
called caspases, as well as activation of nucleases, that results in coordinated enzymatic
breakdown of cellular components
- Cells shrink and “bleb” (form lobules) – cell membrane does not rupture, resulting in
self-contained membrane-bound fragments as the cell self-destructs; lobules are then
phagocytized by surrounding cells
- Useful in embryonic development with cellular pruning (removal of superfluous cells
not needed or those cells that stop functioning) and keeping cancer cells (as well as
virally-infected cells) in check
- When out of control, can lead to neurodegenerative disorders (e.g. Alzheimer’s,
Parkinson’s, Lou Gehrig’s and Huntington’s Disease)
- When non-operational, can lead to the unimpeded proliferation of cancer cells