Chapter 11 CELL COMMUNICATION

Cell-to-cell communication is essential in multicellular organisms.

Cells must communicate in order to coordinate their activities in order to develop, grow and
reproduce.
OVERVIEW OF CELL SIGNALLING
The example of yeast.
Yeast has two sexes or mating types called a and .
Cells of type a secrete a signal called the a factor; those of type secrete a signal called the
factor.
Each factor is secreted to the environment and inds to receptors on the other cell type, e. g. a
type cells have receptors for factors and vice versa.
This causes the cells to move and grow towards one another and eventually fuse. The new cell
has now all the genes of oth parents, a comination that provides greater advantage of
adaptation.
The process y which a signal on a cell!s surface is converted to a specific response is a series
of steps called signal-trans!ction "at#$a%.
Local an long-istanc& signaling.
1" 'aracrin& signaling# The signals are molecules secreted y a cell called local regulators.
These local regulators influence cells in the vicinity. These chemical signals are released into
the extracellular fluid and ad$acent cells respond to a local regulator. The influenced, responding
cells are called targ&t c&lls.
%" S%na"tic signaling# a nerve cell releases n&!rotrans(itt&r (ol&c!l&s into a synapse, the
narrow space etween the transmitting nerve cell and the target cell.
&" )or(onal signaling# 's a long distance signaling. The speciali(ed secreting cells, endocrine
cells, release the chemical signals or regulators into the lood, which distriutes the hormones
throughout the ody.
)nimal and plant cells have cell $unctions and plasmodesmata that allow direct communication
etween ad$acent cells y letting signals flow from one cell to the next through these channels.
The target cell must have the proper type of receptors in order to recogni(e the signal.
STAGES IN CELL SIGNALING.
*eceptors are located in the plasma memrane of the target cells.
+hen reception occurs at the plasma memrane, a pathway of several steps is initiated, which
rings a change in a molecule which in turn causes a change in an ad$acent molecule and so
on. The last molecule in the se,uence rings aout the response.
1" R&c&"tion# the signal molecule inds to an integral protein in the plasma memrane.
%" Trans!ction# the inding of the signal causes a configurational change in the memrane
protein, which initiates the process. Transduction can occur in one step or several steps. The
intermediate molecules in the transduction pathway are called r&la% (ol&c!l&s.
&" R&s"ons&# in the final stage, an en(yme is activated that causes a response. The response
could the catalysis of a reaction, the rearrangement of the cytos-eleton or the activation of a
gene.
SIGNAL RECE'TION
The signal protein matches the shape of a specific site on the receptor protein.
The signal protein acts as a ligan, a small protein that specifically inds to a large one.
The inding of the signal protein causes a conformational change in the receptor protein, which
in turn can now activate another molecule.
.ost signal proteins are water solule and too large to pass through the plasma memrane.
A. Intrac&ll!lar r&c&"tors
/ome signal receptors are proteins found in the cytosol of the cell.
St&roi #or(on&s are small lipid solule hormones that pass through the plasma memrane.
The hormone inds to a receptor protein in the cytosol and activates it.
The hormone-receptor complex enters the nucleus and inds to specific genes.
0enes are activated and messenger *1) is synthesi(ed.
m*1) codes for a protein that causes changes in the ody.
m*1) is translated into a specific protein.
*. R&c&"tors in t#& "las(a (&(+ran&
.ost signal receptors are plasma memrane proteins.
These receptors transmit information from the extracellular environment to the inside of the cell
y changing shape or aggregating when a specific ligand inds to it.
,. G-"rot&in-lin-& r&c&"tors
The G-"rot&in-lin-& r&c&"tors are plasma memrane receptor proteins that wor- with the
help of protein called the G "rot&ins.
These receptor proteins have signal-inding sites facing the extracellular fluid, and 0-inding
sites facing the cytosol.
The 0 protein is inactive when the nucleotide g!anosin& i"#os"#at&. G/', is attached and
active when the g!anosin& tri"#os"#at&. GT', is attached.
*ememer that guanine is nitrogenous ase also found in nucleic acids.
+hen the signal ligand inds to the extracellular site of the receptor protein, it changes shape
and its cytoplasmic side inds to an inactive 0 protein.
The 0 protein is inactive when ound to 023. +hen the 0 protein inds to the receptor, the 0
protein then releases the attached 023, which is replace y a 0T3 from the cytosol, and
ecomes activated.
The active 0 protein travels through the plasma memrane and inds to and activates an
en(yme.
The active en(yme triggers the next step in the pathway, and 0T3 hydrolyses a phosphate and
returns to the inactive 023.
)ll these changes occur in the plasma memrane.
0. T%rosin&--inas& r&c&"tors
) receptor tyrosine -inase can trigger more than one signal transduction pathway at once,
helping the cell regulate and coordinate many aspects of cell growth and reproduction.
) -inase is an en(yme that catalyses the transfer of phosphate groups.
Tyrosine -inase receptors are transmemrane proteins consisting of an extracellular signal
inding site, a transmemrane 4 helix and an intracellular tail containing many tyrosines, an
amino acid.
The cytoplasmic portion of the receptor functions as the en(yme t%rosin& -inas&.
'n the asence of a signal, tyrosine--inase receptors exist as single polypeptides in the plasma
memrane.
The receptor is activated in two steps#
The ligand inding causes the receptor polypeptides to aggregate and form a dimer.
The aggregation causes the activation of the tyrosine--inase part of oth polypeptides y
adding phosphates to the tyrosine ))s on the tail of the polypeptides.
)T3 supplies the phosphates.
*elay proteins in the cytoplasm of the cell recogni(e and ind to the activated tyrosine -inases,
and ecome activated in turn.
5ne dimer may activate ten or more relay proteins. The relay proteins may or may not ecome
phosphorylated.
The activated relay proteins in turn trigger many transduction pathways and responses.
1. Ligan-gat& ion c#ann&l r&c&"tors
'on channels are transmemrane proteins that open forming pores that allow the flow of a
specific -ind of ion across the memrane.
The ligand-gated ion-channel receptors change their configuration and open or close in
response to a specific signal.
This response of the channel protein leads to change in the ion concentration inside the cell.
)t a synapse etween nerve cells, the ion concentration may trigger an electrical signal that is
propagated down the receiving cell.
SIGNAL TRANS/UCTION 'AT)WA2S
)t each step in a pathway, the signal is transduced into a different form, commonly a
conformational change in a protein.
,. 'rot&in "#os"#or%lation
The addition of a phosphate in order to activate an en(yme is a widespread mechanism in
regulating protein activity.
The general name of an en(yme that transfers phosphate groups from )T3 to a protein is
"rot&in -inas&.
.ost cytoplasmic protein -inases act on other sustrate molecules.
.ost -inases phosphorylate their sustrate on either of two amino acids, serine or threonine.
The addition of a phosphate changes the protein from inactive to active.
)ctivation is always associated with change in conformation.
) cascade of protein phosphorylation transmits the signal.
Each phosphorylation causes a conformational change that rings aout the next
phosphorylation and change inactivity.
)t the end of the cascade, a protein is activated that rings aout the response.
'rot&in "#os"#atas&s remove phosphate groups from active proteins ma-ing them availale
for reuse.
0. S&con (&ss&ng&r
Cyclic AMP
Certain small molecules and ions are involved in the transduction pathway and are called
s&con (&ss&ng&rs.
The extracellular signal is the 6first messenger.6
7irst messenger 8signal" comines with receptors on the plasma memrane of the target cell.
The plasma memrane has 0-protein lin-ed receptors.
0-protein lin-ed receptor activates a 0 protein.
0 protein releases 023 and then inds with 0T3.
9inding 0T3 produces a conformational change in the 0 protein and inds it to a&n%l%l
c%clas&, an en(yme emedded in the plasma memrane.
The activated adenylyl cyclase cataly(es the conversion of )T3 to cyclic ).3, c).3, a
secondary messenger.
Cyclic ).3 8c).3" activates one or more en(ymes 8protein -inases" in the cytosol that alter the
activity of the cell.
3rotein -inases phosphorylate a specific protein.
These activated proteins then trigger a chain reaction leading to a metaolic effect.
There are G "rot&in s%st&(s that in#i+it rather than activate adenylyl cyclase in the plasma
memrane.
) signal molecule activates a different receptor that in turns activates an in#i+itor% G "rot&in.
'n the asence of a signal, e.g. epinephrine, Cyclic ).3 is ,uic-ly converted to ).3 y the
en(yme phosphodiesterase.
Calcium ions and inositol triphosphate, IP3.
Cytosolic Ca
%:
concentration is increase y several signals li-e neurotransmitters, some
hormones, and growth factors.
Ca
%:
is a common second messenger. 'ncreasing the concentration of Ca
%:
rings aout many
cell responses, e. g. muscle contraction, cell division and secretion of certain sustances in
animals; greening in response to light, in plants.
Ca
%:
is used as a second messenger in 0 protein pathways and tyrosine pathways.
The concentration of Ca
%:
is much lower in the cytosol than in the extracellular environment of
the cell.
Ca
%:
are actively concentrated in the E* and sometimes into the mitochondria and chloroplasts.
;ormone-receptor complex activates the 0 protein.
0 proteins then activate the memrane ound en(yme phospholipase C.
3hospholipase C splits the phospholipid 3'3% into '3& 8inositol triphosphate" and 2)0
diacylglycerol". 9oth act as s&con (&ss&ng&rs.
'3& stimulates the E* to release calcium, which comines with calmodulin in the cytosol of the
cell.
Calmodulin-Ca complex stimulates protein -inase C to phosphorylate certain proteins.
Calcium is a t#ir (&ss&ng&r in this case.
'n summary# Ca
%:
and inositol triphosphate, '3&.
+hen a hormone inds to a receptor, Ca
%:
channels open and calcium ions move into the
cell.
Certain receptors are lin-ed y a 0 protein to calcium ion channels.
Calcium in the cell inds to the protein calmodulin and changes conformation.
The activated calmodulin then activates certain en(ymes.
CELLULAR RES'ONSES TO SIGNALS
/ignal transduction leads to the regulation of one or more cellular activities. The response may
occur in the cytoplasm or may involve action in the nucleus.
En(ymatic activity
Cytos-eleton rearrangement
0ene activity and m*1) synthesis
.any signaling pathways regulate not the activity of the en(yme ut the synthesis of the
en(ymes or other proteins.
0rowth factors and certain animal and plant hormones regulate the activity of genes.
Signal amplification
/ignal amplification occurs when in a cascading pathway, the numer of activated molecules is
much greater than in the previous step.
The activated proteins persist in their active form long enough to act on many sustrate
molecules efore they ecome inactive. This has a multiplying effect at each step of the
transduction process.
'n this way, a small numer of signal molecules, e.g. epinephrine, can lead to the release of
hundreds of millions of molecules.
Specificity of cell signaling
The particular comination of proteins in a cell gives the cell great specificity in oth the signals
it detects and the responses it carries out.
Cells in different tissues will respond or not to a particular signal molecule; cells in different
tissues may respond to the same signal ut the response is different in each tissue.
Epinephrine causes the heart to contract and the liver to rea- down glycogen.
The response depends on the collection proteins found in each cell.
*ranc#ing "at#$a% and 3cross-tal-3 int&raction are important in regulating signal
transduction#
) pathway diverges to produce two responses# ranching pathway.
Two pathways triggered y different signals converge to produce a single response#
activation of inhiition of a protein.
See fig 11.15
Scaffolding proteins and signaling complexes
)dapter<scaffolding proteins have no ovious catalytic function, and act to assemle other
components into the signaling complex, e. g. -inases.
/caffolding proteins increase signal-transduction efficiency y holding multiple components of a
pathway together.
/caffolding proteins are relay proteins that have the aility to ind to the receptor protein on one
end and to several other relay proteins at the other end.
The receptor proteins ecome simultaneously attached to the scaffolding protein. 5nce the
scaffolding protein is activated y the memrane receptor, the several relay proteins ound to it
ecome activated in turn.
/ome scaffolding proteins in rain cells permanently hold together networ-s of signaling-
pathway proteins at synapses. This enhances the speed and accuracy of the signal transfer
etween cells.
/ome proteins may participate in more than one pathway, either in different cell types or in the
same cell at different times or under different conditions.
Termination of the signal
'f a transduction pathway ecomes loc-ed into one state, the conse,uences could disastrous,
e.g. case of cholera.
The inding of a signal to a receptor is reversile.
+hen the signal molecule leaves the receptor, the receptor reverts ac- to its inactive form.
There are a variety of ways in which relay proteins revert to their inactive forms, e.g. en(ymes
that remove phosphates 8phosphatases".