Cell Communication and

Signaling
At the end of this course you should be able to think
like a cell that needs to talk
 Cell Communication and
Signaling
At the end of this course you should be able to think
like a cell that needs to talk
 Week 2: Components of cell
signaling; Stages in cell comm.
Signaling components
• A signaling cell
• Uses many different forms of signals compounds
• Could be proteins or gases, tethered to the PM or unbound
• Seeks to effect a change in the behavior of the responding cell

• A responding/target cell
• Is receptive to signaling cell
• Utilizes a receptor to “accept” the signal. Describe in general, how this is done. Conc, affinity, etc.
• More to come later in the semester
• Touch on receptor types, ligand types, etc.
• Receptors help overcome an important biophysical problem: The lipid bilayer

• A signaling molecule
• More detailed here:
• Gases,
• Protein
• Membrane-bound
• GPCRs, etc
The phospholipid bilayer
Types of cell communication
• Autocrine
• Self activation
• Example…
• Cell-cell contact
• Notch signaling as exemplar
• Very important during development
• Paracrine
• Short distance acting/local
• Regulatory mechanisms prevent the diffusion of molecules beyond their targets: E-Matx, extracellular
enzymes and/or duffusion by local targets; low conc at start
• Example FGF signaling during development of trachea and vascular system, also axon pathfinding slit oand
robo
• Endocrine
• Hormonal/long distance
• Carried in blood or bodily fluids to target cells which are usually far away
• What mechanisms regulates the communication?
• Example: sex hormone, receptivity, insulin response, glucose metab, etc
Another way to think about communication
types
Short Distance Long Distance
• Autocrine • Endocrine
• Cell-cell contact • Hormone travel through the blood

• Paracrine • Neurotransmission
• Action potential
• Very fast
Autocrine signaling
Schematic illustration
Autocrine signaling

DLBCL coexpressing high levels of VEGF and VEGFR-1 may be dependent on autocrine signaling for survival or proliferation.
A hypothetical model of a lymphoma cell expressing high levels of VEGF and VEGFR-1. (a) High levels of VEGF mRNA are
transcribed and VEGF protein is secreted locally, binds cell-surface VEGFR-1, and initiates intracellular survival and/or
proliferation signaling cascades. (b) The autocrine feedback loop may be 'private,' and thus may be accessible to cell
permeable VEGFR-1 tyrosine kinase inhibitors but not recombinant proteins that act as extracellular VEGF sinks.
(c) Components of standard anthracycline-based chemotherapy such as doxorubicin may interrupt this autocrine feedback
loop, perhaps by inhibiting transcription of VEGF mRNA, leading to decreased proliferation signals and/or increased apoptosis.

Gratzinger et al. 2008 Lab Invest 88(1):38-47

Autocrine signaling is important during
development and in tumor growth
• Autoreceptor function is key

• Involves a cell signaling to itself

• And to identical cells of the same type

• One mechanism through which cancer cell bypass the cells regulation
of cell proliferation
Cell-cell contact
Cell-cell contact mediated signaling

Ligand binding to it receptor initiates a downstream cascade that in the case of notch results in cell proliferation
The notch example

• Essential signaling pathway

during cell proliferation and
development
• Notch receptor binding to delta
initiates downstream cascade
that results in neural cells to
promote cell proliferation
Paracrine signaling
Schematic representation
 Autocrine and paracrine
signaling provides mechanistic
basis for tumor communication
Beristain et al. 2012. J Cell Science. 125(4): 943-955
 Key example of paracrine
signaling
Tumor cell communication with stromal cells (connective tissues e.g.,
fibroblasts) provides important signal that promotes tumor growth
The tumor microenvironment is quite
heterogenous
• Hypoxia
• Increased lactate formation via glycolysis
• Low oxygen environment
• Extracellular acidification
• Intracellular alkalinization
• Abundance of growth factors
• VEGF
• EGFR
Endocrine signaling
Schematic representation and chalk talk
Endocrine signaling
• Hormonal regulation

• Signaling molecules, hormones, act over a distance

• Carried via blood stream

• Target cells are distributed throughout the body

• Testosterone, estrogen, insulin

Adrenaline and fight or flight
Discussion
Recap of Lecture
Journal Club
 Cell autonomous vs. non-cell autonomous effects
Cell autonomous
• Cell autonomous: an effect
originates and ends within a cells
• Non-cell autonomous: an effect
originates in a cells migrates or
spreads to other cells vis secretion,
diffusion, cell-cell contact, etc
• A morphogen, molecules that act Cell non-autonomous
on cells (usually during
development) in a concentration
dependent manner to induce a to
induce a cellular effect, e.g.,
activation or repression of gene
expression