Cell biology and
immunology
1, Cell signaling:
Cell signaling is important for cell to cell communication and for sensing and
interacting with the extracellular- or intracellular environment.
There are four kinds or intracellular signaling:
- Contact dependent: they have to physically connect. It is short distant and
is important in embryonic development and immune responses.
- Paracrine communication: one of the cell secretes a signal molecule that
can only travel short distances. So, it is still short range and is important in
inflammation response.
- Synaptic communication: using the neuron to send a signal with
neurotransmitters. It is long range, depending on how long the axon is.
- Endocrine communication: uses hormones as signal molecules, that can
travel long distances. These are secreted into the blood stream. Examples
are insulin and adrenaline.
Receptors:
There are three main kinds of extracellular receptors.
Only large and hydrophilic, it cannot pass through the
membrane and must bind to one of these:
- Ion-channel coupled receptor: ligands can be;
neurotransmitters or second messages.
- They are known for their extracellular ligand-gated
pore. Ligand binding induces the opening or the
closing of a channel that relates the influx of ions.
An example is the acetylcholine binding sites in the
synaptic cleft. It consists of 5 subunits.
- G-protein coupled receptor: ligands can be;
neurotransmitters, proteins, peptides, hormones
are derivatives of amino acids and fatty acids.
- It has exactly 7 transmembrane helices, which
makes them very recognizable. A ligand will bind to the receptor, which will
release the G-coupled protein, this will then work as a second messenger.
- Enzyme-coupled receptor: the ligand will coupled to an enzyme. It is
known for their intracellular kinase domain. Ligands are mainly signal protein
ligands, like insulin and growth factors.
- It works like this, a ligand binds and this causes dimerization (meaning: the
two parts of the receptor join together). This leads to the phosphorylation of
the receptor, that can then work as a scaffolder to recruit additional proteins.
,And there is one type of
intracellular receptor. If the signal
is a small and hydrophobic
molecule (like steroids or gases),
it can pass through the membrane
and bind to:
- Nuclear receptor
One signal can create different
responses based on the receptor
it binds to. Like acetylcholine, it
can cause an increase of decrease
in heart rate, it can cause
secretion of saliva and it can cause muscles to contract.
It is also never just one signal the sends a response, it is rather a combination
of signals.
Regulation of signaling proteins:
Signaling proteins are the product of a when a receptor is activated, it is all
intracellular.
Binding mediated regulation:
- Ligand binding: the extracellular proteins I discussed earlier are examples
of this.
- Protein binding: second messaging is an
example of protein binding. A regulatory protein
can bind to an active protein to make it inactive,
or it can bind to an inactive protein to make its
active. cAMP is an example of a regulatory
protein.
Enzymatic regulation:
- GTP hydrolysis: a cell is inactive when it is
bound to GDP, but when GTP is added, this
replaces the GDP and the cell becomes active.
This is regulated with GEF and GAP. GEF
(Guanine nucleotide Exchange Factor) actives
the cell by adding GTP. And GAP (GTPase
activating protein) actives GTPase, which
deactivates the cell.
- G coupled proteins can function as a GEF.
- Post-translational modifications: when a protein gets phosphorylated, it
changes its function. The three amino acids that can be phosphorylated are;
serine, tyrosine and threonine.
,- When a protein is phosphorylated, a ubiquitin can bind to it. This changes
the function of the protein.
Thee polyubiquitylation is made this way:
Cell signaling in a crowded environment:
A cell is a very crowded environment, it is never just one protein floating
around. The cell has a few solutions to keep organized:
- high affinity: this means that the ligand most will bind very strongly. Once
activated, it is always on, because they don’t let go easily.
- Multiple weaker interacting: signal proteins interact with their target via
multiple interactions.
- Colocalization: using a scaffolding protein to recruit the signal and target
proteins.
- Allosteric binding/ multistep processes: basically, using multiple steps,
like second messengers.
, 2, Cytoskeleton:
The cytoskeleton gives the cell its; shape, strength, ability to move and cell
origination/transport. It consists of actin, microtubules and intermediate
filaments.
The cytoskeleton is constantly remodeled, totally nothing like a bone like the
name implies. The actin always moves towards the nucleus, to help move the
cell.
Actin filaments:
Consist of two stranded alpha helixes, its function is for; shape, locomotion,
contractility and cytokinesis. It is the most abundant protein in the cell. And it
can come in four different shapes;
One actin filament double stranded helix always has a plus end and a minus
end. An ATP can bind to both ends, it then hydrolyses to ADP. The ADP easily
diffuses away so a new ATP can bind.
This is done so that the filament can grow.
How fast this happens depends of how fast an ATP-bound monomer binds to
the filament, which depends on the association rate (Kon) and the amount
of free monomers (Cactin).
It also depends of how fast the ADP-bound monomer leaves, which depends on
the disassociation constant (Koff).
When the ATP binds as fast as the ADP leaves, the filament neither grows nor
shrinks. This is the critical concentration (Cc). The Cc can be devided into
Cc plus and Cc minus.
So if, Cc plus < Cactin < Cc minus, the filament grows on the minus side and
shrinks on the plus side. This is called treadmilling.
Different actin filaments can be stuck together on a 70 degrees angle (like the
dendritic network), because of Arp2 and Arp3. Both Arp2 and Arp3 are
structurally very similar to actin and can thus bind to it very easily.
Myosin II: is important for muscle contraction. It is an actin-based motor
proteins.
Muscles consist of actin and myosin, and to contract muscles you want to
overlap them. This happens basically in 5 steps;
1. The myosin head is attached to the actin.
immunology
1, Cell signaling:
Cell signaling is important for cell to cell communication and for sensing and
interacting with the extracellular- or intracellular environment.
There are four kinds or intracellular signaling:
- Contact dependent: they have to physically connect. It is short distant and
is important in embryonic development and immune responses.
- Paracrine communication: one of the cell secretes a signal molecule that
can only travel short distances. So, it is still short range and is important in
inflammation response.
- Synaptic communication: using the neuron to send a signal with
neurotransmitters. It is long range, depending on how long the axon is.
- Endocrine communication: uses hormones as signal molecules, that can
travel long distances. These are secreted into the blood stream. Examples
are insulin and adrenaline.
Receptors:
There are three main kinds of extracellular receptors.
Only large and hydrophilic, it cannot pass through the
membrane and must bind to one of these:
- Ion-channel coupled receptor: ligands can be;
neurotransmitters or second messages.
- They are known for their extracellular ligand-gated
pore. Ligand binding induces the opening or the
closing of a channel that relates the influx of ions.
An example is the acetylcholine binding sites in the
synaptic cleft. It consists of 5 subunits.
- G-protein coupled receptor: ligands can be;
neurotransmitters, proteins, peptides, hormones
are derivatives of amino acids and fatty acids.
- It has exactly 7 transmembrane helices, which
makes them very recognizable. A ligand will bind to the receptor, which will
release the G-coupled protein, this will then work as a second messenger.
- Enzyme-coupled receptor: the ligand will coupled to an enzyme. It is
known for their intracellular kinase domain. Ligands are mainly signal protein
ligands, like insulin and growth factors.
- It works like this, a ligand binds and this causes dimerization (meaning: the
two parts of the receptor join together). This leads to the phosphorylation of
the receptor, that can then work as a scaffolder to recruit additional proteins.
,And there is one type of
intracellular receptor. If the signal
is a small and hydrophobic
molecule (like steroids or gases),
it can pass through the membrane
and bind to:
- Nuclear receptor
One signal can create different
responses based on the receptor
it binds to. Like acetylcholine, it
can cause an increase of decrease
in heart rate, it can cause
secretion of saliva and it can cause muscles to contract.
It is also never just one signal the sends a response, it is rather a combination
of signals.
Regulation of signaling proteins:
Signaling proteins are the product of a when a receptor is activated, it is all
intracellular.
Binding mediated regulation:
- Ligand binding: the extracellular proteins I discussed earlier are examples
of this.
- Protein binding: second messaging is an
example of protein binding. A regulatory protein
can bind to an active protein to make it inactive,
or it can bind to an inactive protein to make its
active. cAMP is an example of a regulatory
protein.
Enzymatic regulation:
- GTP hydrolysis: a cell is inactive when it is
bound to GDP, but when GTP is added, this
replaces the GDP and the cell becomes active.
This is regulated with GEF and GAP. GEF
(Guanine nucleotide Exchange Factor) actives
the cell by adding GTP. And GAP (GTPase
activating protein) actives GTPase, which
deactivates the cell.
- G coupled proteins can function as a GEF.
- Post-translational modifications: when a protein gets phosphorylated, it
changes its function. The three amino acids that can be phosphorylated are;
serine, tyrosine and threonine.
,- When a protein is phosphorylated, a ubiquitin can bind to it. This changes
the function of the protein.
Thee polyubiquitylation is made this way:
Cell signaling in a crowded environment:
A cell is a very crowded environment, it is never just one protein floating
around. The cell has a few solutions to keep organized:
- high affinity: this means that the ligand most will bind very strongly. Once
activated, it is always on, because they don’t let go easily.
- Multiple weaker interacting: signal proteins interact with their target via
multiple interactions.
- Colocalization: using a scaffolding protein to recruit the signal and target
proteins.
- Allosteric binding/ multistep processes: basically, using multiple steps,
like second messengers.
, 2, Cytoskeleton:
The cytoskeleton gives the cell its; shape, strength, ability to move and cell
origination/transport. It consists of actin, microtubules and intermediate
filaments.
The cytoskeleton is constantly remodeled, totally nothing like a bone like the
name implies. The actin always moves towards the nucleus, to help move the
cell.
Actin filaments:
Consist of two stranded alpha helixes, its function is for; shape, locomotion,
contractility and cytokinesis. It is the most abundant protein in the cell. And it
can come in four different shapes;
One actin filament double stranded helix always has a plus end and a minus
end. An ATP can bind to both ends, it then hydrolyses to ADP. The ADP easily
diffuses away so a new ATP can bind.
This is done so that the filament can grow.
How fast this happens depends of how fast an ATP-bound monomer binds to
the filament, which depends on the association rate (Kon) and the amount
of free monomers (Cactin).
It also depends of how fast the ADP-bound monomer leaves, which depends on
the disassociation constant (Koff).
When the ATP binds as fast as the ADP leaves, the filament neither grows nor
shrinks. This is the critical concentration (Cc). The Cc can be devided into
Cc plus and Cc minus.
So if, Cc plus < Cactin < Cc minus, the filament grows on the minus side and
shrinks on the plus side. This is called treadmilling.
Different actin filaments can be stuck together on a 70 degrees angle (like the
dendritic network), because of Arp2 and Arp3. Both Arp2 and Arp3 are
structurally very similar to actin and can thus bind to it very easily.
Myosin II: is important for muscle contraction. It is an actin-based motor
proteins.
Muscles consist of actin and myosin, and to contract muscles you want to
overlap them. This happens basically in 5 steps;
1. The myosin head is attached to the actin.
