Important words and concepts from Chapter 11,
Campbell & Reece, 2002 (1/29/2005):
by Stephen T. Abedon (abedon.1@osu.edu)
for Biology 113 at the Ohio State University
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(1) Chapter title: Cell Communication
(a)
Interactions between organisms can range from cooperative to antagonistic. This is true for single-celled
organisms and even the individual cells that make up multicellular organisms.
As a general rule, cooperation among individuals
(or cells) is more likely (though by no means guaranteed) the more genetically
similar the cells or individuals are, with nearly complete cooperation
occurring particularly when organisms (or cells) are genetically identical plus
dependent upon one another for their replication (thereby one cell making
babies in a genetic sense is making babies for every genetically identical
cell).
(b)
Such is the case among the cells that make up most multicellular
organisms, and cell-to-cell communication represents how such cells coordinate
their physiological behaviors so as to create a cooperative whole, one that is
greater than the sum of their cellular parts. This chapter combines bits of
endocrinology (the study of hormones), cell biology, and biochemistry to introduce the complexities of
the cooperative molecular interactions between cells. When cell-to-cell
communication is unsuccessful, a result can be a harmful absence of
cooperation, a.k.a., defection, which between cells within a multicellular
organism we might recognize as tumors or cancer, as adult-onset diabetes, as
developmental abnormalities, etc.
(c)
[cell communication
(Google Search)] [index]
(a)
Most cell-to-cell communication involves some kind of chemical
signaling, including
(i)
Chemicals that are allowed to freely diffuse between cells,
(ii)
Chemicals that are received by a cell only given cell-to-cell contact,
and
(iii)
Chemicals that freely diffuse from one cell’s cytoplasm to another’s via junctions directly linking the
cytoplasms of adjacent cells.
(b)
See Figure 11.3, Local and
distant cell communication in animals
(c)
See Figure 11.4,
Communication by direct contact between cells
(d)
Signals can be purposeful in the sense that one cell is sending off a
signal meant to be received and interpreted in a
certain way by another cell (e.g., a hormone)
(e)
Alternatively, signals can be byproducts of cellular metabolism that
one cell releases essentially as waste or without intending (in an evolutionary
algorithm sense) to initiate a signal to another cell, but nevertheless other
cells are capable of interpreting those signals and acting on them (e.g., the
release of lactic acid from an anaerobically exercising
muscle cell)
(f)
This chapter considers particularly signaling that involves chemicals
that are purposefully released from
one cell and allowed to freely diffuse to a second (or more) recipient cell(s)
in an act of communication that is deliberately initiated, received, and interpreted
in order to increase the physiological coordination of the cells of a
multicellular organism
(g)
In addition, this chapter’s emphasis is particularly on those events
that occur following reception of a chemical signal rather than on the purpose
of the signal or why and how a given cell released the signal
(h)
[chemical signaling
(Google Search)] [index]
(a)
A local regulator is a chemical signal
that influences only neighboring cells
(b)
Within an animal this would imply a lack of systemic diffusion
which, in turn, suggests that the local regular is not released into the blood
or the lymph (which are the routes to systemic diffusion) but instead into the
intercellular space/extracellular matrix
(c)
Among the localities in which local regulators are active is within the
small gaps (called synapses) that occur between nerve cells and between nerve
and muscle cells
(d)
["local regulation"
cell or cells (Google Search)] [index]
(a)
Unlike local regulators, hormones are chemical signals that diffuse systemically (e.g., diffusion
through and are carried by blood and lymph as well as the intercellular space/extracellular matrix)
(b)
[hormone or hormones
(Google Search)] [hormone search (The Dictionary of Cell and Molecular Biology)] [index]
(5) Three stages of cell signaling (signal-transduction pathway)
(a)
Local regulators or hormones are
released by cells, received, and then acted upon by other cells
(b)
We can biochemically
differentiate the reception, etc. of these chemical signals into three stages:
(i)
Reception (by a cell)
(ii)
Transduction (from outside of the cell to inside the cell,
etc.)
(iii)
Response (how the cell responds to having received the signal)
(c)
See Figure 11.5, Overview of
cell signaling
(d)
Most of this chapter is devoted to discussing the complexity of these
processes, with particular emphasis on transduction
(e)
Note that this signal transduction is simply one of the
many highly complex processes one studies when considering the cell biology (and biochemistry) of the cells of multicellular
organisms
(f)
[signal transduction pathway,
signal transduction pathways
(Google Search)] [index]
(a)
Reception of a chemical signal literally involves the attachment (or
association) of the chemical signal to some aspect of the recipient cell’s plasma membrane
(b)
The means of reception, typically involving a membrane protein, may be intimately linked to
the existence of an intact plasma membrane
(c)
A membrane is thus a requirement for the occurrence of subsequent signal transduction and response (i.e., cell-to-cell signaling
typically requires that recipient cells are intact)
(d)
[signal reception cell
(Google Search)] [index]
(7) Transduction (signal transduction)
(a)
There exist three stages of cell signaling,
a beginning,
a middle, and an end
(b)
Signal reception
represents the beginning while transduction represents the middle
(c)
Transduction is the conversion of the reception signal, typically found
at the surface of the cell, to a signal that directly facilitates a response
(d)
Very often signal transduction involves a number of steps that, taken
as a whole, can be somewhat complex (perhaps overwhelmingly so)
(e)
Though not explaining the complexity, nevertheless a basic purpose of
the need for signal transduction — linking reception and response — is that the
plasma membrane receptor and the molecules involved in formulating a response
are not always (rarely?) located in the same region of the cell; thus
intracellular signals (often chemical) serve to physically connect reception
and response
(f)
For example, a signal-transduction pathway
may involve the following:
(i)
Reception (at the plasma membrane) à
(ii)
Transduction (through the cytoplasm) à
(iii)
Response (in the nucleus, e.g., transcription)
(g)
[signal transduction
(Google Search)] [index]
(a)
The response to cell signaling varies enormously, depending on the
signal as well as the receiving cell
(b)
Suffice it to say that responses typically involve either the turning
on of a specific (often enzymatic) activity (including the synthesis of new enzymes)
or a reduction in (or turning off of) a specific enzymatic activity
(c)
In addition, a response can involve the turning on or off of more than
one activity
(d)
“Explanation for the specificity exhibited in cellular responses to
signals is the same as the basic explanation for virtually all differences
between cells: Different kinds of cells
have different collections of proteins. The response of a particular cell
to a signal depends on its particular collection of signal receptor proteins,
relay proteins, and proteins needed to carry out the response.” (p. 202, Campbell et al.,
1999)
(e)
For the sake of discussion throughout this chapter, consider response
to be simply some end point of a signal-transduction pathway
(a)
“Most signal molecules are water-soluble and too large to pass freely through the plasma membrane… A cell targeted by a
particular chemical signal has molecules of a receptor
protein that recognizes the signal molecule. The signal molecule is
complementary in shape to a specific site on the receptor and attaches there,
like a key in a lock—or like a substrate in a catalytic site of an enzyme. The signal
molecule behaves as a ligand, the
term for a small molecule that specifically binds to a larger one. Ligand
binding generally causes a receptor protein to undergo a change in
conformation—that is, to change shape. For many receptors, this shape change
directly activates the receptor so that it can interact with another
cellular molecule. For other kinds of receptors… the immediate effect
of ligand binding is more limited, mainly causing the aggregation of two or
more receptor molecules.” (p. 192, Campbell et al., 1999)
(b)
Membrane-protein signal receptors come in
a variety of types including:
(i)
G-protein-linked receptors
(ii)
Tyrosine-kinase receptors
(iii)
Ion-channel receptors
(c)
Some chemical signal molecules, such as steroid hormones, are able to pass through the plasma membrane without the aid of a
membrane-protein receptor, allowing reception and transduction
to be carried out by the same (intracellular) protein
(d)
[ligand, ligand signal, signal receptor (Google Search)] [index]
(10) G-protein-linked
receptors (G
protein) [a.k.a., G-protein coupled receptors]
(a)
G-protein-mediated pathways involve at least three components:
(i)
A G-protein-linked receptor (responsible for reception of the chemical signal)
(ii)
A G protein (responsible for signal transduction)
(iii)
And the protein the G protein activates (responsible either for signal
transduction or directly effecting the response)
(b)
G proteins are signal-transduction proteins that are in an active state when they are bound to a
molecule of GTP (similar to ATP except possessing the guanine purine rather than the adenine purine; see Kreb’s cycle for
another example of the use of GTP in a metabolic pathway)
(c)
G-protein-linked receptors are membrane proteins that interact with a G
protein upon reception of a chemical signal
(d)
The G protein interacts with the receptor on the receptor’s cytoplasmic
side, and conformational changes in the receptor (induced by ligand attachment)
results in the activation of the G protein
(e)
The G protein diffuses to and then activates a subsequent protein in
the signal-transduction pathway (or the protein
that is directly responsible for the response) by
binding to that protein while in its own (the G protein’s) active state
(f)
Subsequently, the G protein hydrolyzes the GTP
(to GDP) which inactivates the G protein and whatever the active G protein had
activated (these activation-after-activation-after-activation pathways can get
complicated)
(g)
The important function of G-protein inactivation is that they allow a
reversibility to the G-protein mediated activation of a protein, thus
contributing to the dynamic nature of a cell
(h)
See Figure 11.7, The
functioning of a G-protein-linked receptor
(i)
[G protein (Google Search)] [G-protein-linked receptors
links (MicroDude)] [index]
(11) Tyrosine-kinase receptors
(a)
Tyrosine-kinase receptors differ from G-protein-linked receptors in three crucial
ways
(i)
Rather than activating G proteins following their conformational change
(that follows ligand binding), tyrosine-kinase receptors instead activate
their own enzymatic activity, the tyrosine-kinase
activity and then phosphorylate themselves—the phosphorylated receptor is then
recognized by cytoplasmic proteins which effect the transduction event through
the cytoplasm
(ii)
Part of the process of activation of tyrosine-kinase activity involves
a dimerization (linking together of two subunits) of the
tyrosine-kinase receptor
(iii)
Individual tyrosine-kinase receptors are often capable of activating
multiple transduction pathways
(b)
See Figure 11.8, The
structure and function of a tyrosine-kinase receptor
(c)
[tyrosine kinase receptors
(Google Search)] [protein kinases in disease (lots of info
but heavy going) (The Protein Kinase Resource)]
[receptor tyrosine kinase search (The Dictionary of Cell and Molecular Biology)]
[index]
(a)
A kinase is an enzyme that phosphorylates another protein
(or, in the case of a tyrosine-kinase receptor, also themselves)
(b)
ATP supplies the phosphate group
(c)
A tyrosine kinase is thus an enzyme that
phosphorylates tyrosine amino acids found on target proteins
(d)
[protein kinases (Google Search)] [phosphoprotein database (a collection of
proteins that are phosphorylated) (Peter V. Hornbeck)] [protein kinases in disease (lots of info
but heavy going) (The Protein Kinase Resource)]
[protein kinase search (The
Dictionary of Cell and Molecular Biology)] [index]
(a)
A protein phosphatase catalyzes the reverse reaction of that catalyzed
by a protein kinase, i.e., the hydrolytic removal
of a phosphate added to a protein
(b)
The important function of protein phosphatases is that they allow a
reversibility to the protein-kinase-mediated phosphorylation of a protein, thus
contributing to the dynamic nature of a cell
(c)
[protein phosphatases
(Google Search)] [index]
(a)
With ion-channel receptors, the molecules responsible for transduction
are ions (e.g., Na+ or Ca2+) that are normally found
outside of cells
(b)
Here binding of a ligand to the receptor (no, the external ions
themselves are not the ligands) results in an opening of a gate through the
plasma membrane that allows entrance of the ions (both gate and receptor are proteins, likely one in the same protein)
(c)
The increased ion concentration in the cytoplasm either
propagates signal transduction or results in a direct stimulation of a response
(d)
Thus,
(i)
Ligand binding (reception) à
(ii)
Channel opening à Ion inflow (transdution)
à
(iii)
Further transduction or response
(e)
See Figure 11.9, A
ligand-gated ion-channel receptor
(f)
[ion-channel receptor or
receptors (Google Search)] [calcium secondary messernger search (The Dictionary of Cell and Molecular Biology)]
[index]
(a)
During signal transduction, signals may be amplified
(b)
Amplification is accomplished by transduction involving a series of enzymes (typically protein kinases)
(c)
Recall that enzymes may catalyze a chemical reaction without being used
up in the process; thus, one activated protein kinase may phosphorylate many
more than one individual target protein (or instead may activate more than one
of the same kind of target protein)
(d)
Such activation allows an exponential increase in the number of
activated proteins (e.g., one protein activates two, which together activate
four, which together activated eight, etc.) which means that the reception of
few ligands
at the cell surface can lead to dramatic changes in enzyme activity within the
cell
(e)
“Keep in mind that the original signal molecule is
not physically passed along a signaling pathway;
in most cases, it never even enters the cell. When we say that the signal is
relayed along a pathway, we mean that certain information is passed on. At each step the signal is transduced
into a different form, commonly a conformational change in a protein. Very
often, the conformational change is brought about by phosphorylation.” (p. 195,
Campbell et al.,
1999)
(f)
See Figure 11.11, A
phosphorylation cascade
(g)
See Figure 11.16,
Cytoplasmic response to a signal: The stimulation of glycogen breakdown by
epinephrine
(h)
See Figure 11.17, Nuclear
response to a signal: The activation of a specific gene by a growth factor
(i)
[signal amplification pathway
(Google Search)] [index]
(a)
A second messenger is a non-protein molecule
that participates in the intracellular transduction of a signal
(b)
“The extracellular signal molecule that binds to the membrane receptor
is a pathway’s ‘first messenger’.” (p. 197, Campbell et al.,
1999)
(c)
A major advantage of second messengers is their small size and water solubility which allows rapid diffusion throughout a
cell’s cytoplasm
(d)
["second messenger"
or "second messengers" (Google Search)] [index]
(a)
Cyclic AMP is an important second messenger
(b)
Cyclic AMP is formed from ATP
and resembles (though is different from) adensosine monophosphate (cAMP
contains a ring that is the result of a dehydration synthesis reaction)
(c)
See Figure 11.12, Cyclic AMP
(d) G-proteins, in certain