Download Cell Cycle, Mitosis and Cytokinesis

Cells
Two categories: (i) simple, non-nucleated prokaryotic cells
(ii) complex, nucleated eukaryotic cells.
Cell Degradation
• Normally worn-out cells are replaced through cell division.
•
In humans, after 52 divisions cell division comes to a halt:
“Hayflick” limit -referred to as senescent.
• Cancer cells, do not degrade in this way. Telomerase, present in
large quantities in cancerous cells, rebuilds the telomeres, allowing
division to continue indefinitely.
Growth factor (GF)
Is a signalling molecules capable of stimulating cellular growth,
proliferation and cellular differentiation.
• Usually it is a protein or a steroid hormone.
• GF is important for regulating a variety of cellular processes- cell
differentiation and maturation.
e.g. cytokines and hormones
• GF is used in the treatment of hematologic and oncologic diseases
and cardiovascular diseases like:
e.g. Neutropenia, myelodysplastic syndrome,leukemias, aplastic
anaemia, bone marrow transplantation etc.
• GF is sometimes used interchangeably with the
term cytokine.
• While GF implies a (+) ve effect on cell division,
cytokine is a neutral term with respect to whether
a molecule affects proliferation.
e.g. some cytokines can be GF: G-CSF and GM-CSF,
but Fas ligand is used as "death" signals causing
apoptosis.
Classes of GF
Individual GF proteins tend to occur as members of larger
families of structurally and evolutionarily related proteins.
e.g.
•
Bone morphogenetic proteins (BMPs)
•
Platelet-derived growth factor (PDGF)
•
Epidermal growth factor (EGF)
•
Thrombopoietin (TPO)
•
Erythropoietin (EPO)
•
Transforming growth factor alpha(TGF-α)
•
Fibroblast growth factor (FGF)
•
Transforming growth factor beta (TGF-β)
•
Hepatocyte growth factor (HGF)
•
Vascular endothelial growth factor (VEGF)
•
Insulin-like growth factor (IGF)
•
Myostatin (GDF-8)
•
Nerve growth factor (NGF) and other
neurotrophins
Growth Factor
Range of Specificity
Effects
Epidermal growth
Broad
Stimulates cell proliferation in many
tissues; plays a key role in
factor (EGF)
regulating embryonic development
Erythropoietin
Narrow
Required for proliferation of red blood cell
precursors and their
maturation into erythrocytes (red blood
cells)
Fibroblast growth
Broad
factor (FGF)
Initiates the proliferation of many cell
types; inhibits maturation
of many types of stem cells; acts as a
signal in embryonic
development
Insulin-like
Broad
Stimulates metabolism of many cell types;
potentiates the effects of other growth
factors in promoting cell proliferation
Narrow
Triggers the division of activated T
lymphocytes during the immune response
growth factor
Interleukin-2
Characteristics of Growth Factors
• Over 50 different GF have been isolated . A specific
cell surface receptor “recognizes” each growth factor,
its shape fitting that growth factor precisely. When
the growth factor binds with its receptor, the
receptor reacts by triggering events within the cell.
• Some growth factors, like PDGF and epidermal
growth factor (EGF), affect a broad range of cell
types, while others affect only specific types.
Growth
• Implies development, from the time of birth to the time
of maturity and for many species, beyond maturity to
eventual senescence or death.
• Increase in size, height and mass resulting from cell
multiplication and cell expansion, as well as
maturation of tissues.
• Also necessitates programmed cell death, leading to
the production of the final body form.
Cell division
• Growth is a steady, continuous process,
interrupted only briefly at M phase when
the nucleus and then the cell divide in two.
• Cell division/cell cycle, has four major parts
– G1 phase , S phase, G2 phase and M phase
Phases in a
Cell cycle
1h
12 h
Phases of the cell cycle
other than mitosis, is
often termed as
12 h
interphase (12 - 36h)
7h
Cell cycle
The cell cycle of eukaryotic cells can be divided into four successive
phases:
(i) M phase (mitosis): (1-2 h)
•
The nucleus and the cytoplasm divide
•
Cell growth and protein production stop at this stage
•
Nuclear division (karyokinesis) and cytoplasmic division (cytokinesis),
accompanied by the formation of a new cell membrane.
•
Physical division of "mother" and "daughter" cells.
•
M phase has - prophase, prometaphase, metaphase, anaphase and
telophase leading to cytokinesis.
• Focused on the complex and orderly
division into two similar daughter cells.
• There is a Metaphase Checkpoint that
ensures the cell is ready to complete cell
division.
(ii) S phase (DNA synthesis):
The DNA in the nucleus replicates (once
only)
Cell cycle
(iii & iv) Two gap phases, G1 & G2.
– The G1 phase is a critical stage, allowing
either commitment to a further round of cell
division or withdrawal from the cell cycle
(G0) to embark on a differentiation pathway
Cell cycle
• G1 phase is also involved in the control of
DNA integrity before the onset of DNA
replication.
• Synthesis of enzymes for nucleotide and
nucleic acid biosynthesis takes place in
this phase
Cell cycle
– G2 phase:
The cell checks the completion of DNA replication and
the genomic integrity before cell division starts.
Protein and RNA synthesis that takes place in the S
phase continues to the G2 Phase
significant protein synthesis occurs during this phase,
mainly involving the production of microtubules, which
are required during the process of division, called mitosis.
Control of cell cycle
Note the 3 main sites
Control of the Cell Cycle
Check points: Quality Control of the Cell Cycle
• Eukaryotic cells have gene products that govern
the transition from one phase to the other.
• These are family of proteins in the cytoplasm
e.g. Cyclins
• Their levels in the cell rise and fall with the
stages of the cell cycle.
Check points
• They turn on different cyclin dependent Kinase
(CDKs) and Cell division cyclin kinase (CdCK)
that phosphorylates substrate essential for
progression through the cycle.
• These ensure that all phases of the cell cycle
are executed in the correct order.
Cyclins and CDKs involved in cell cycle
progression
Phase
Cyclin
Kinase
Function
G1
Cyclin D
S
Cyclin E & A
CDK2
Initiation of DNA
synthesis in early S
phase
M
Cyclin B & A
CDK1
Transition from G2 to
M
CDK 4 & 6 Cell cycle
progression- passing
G1/S boundary
Check points
• CDK levels in the cell remain fairly stable, but
each must bind the appropriate cyclin (whose
levels fluctuate) in order to be activated.
• CDK act by adding phosphate groups to a
variety of protein substrates that control
processes in the cell cycle.
Cyclin
• Cell cycle is controlled by various proteins
regulated by the Genes catalytic and target
(Cyclin) unit
• The cyclin units appear transiently at
various sites and disintegrate after passing.
G1
Start
S
G2
M
G1
CDK
S PHASE
CYCLIN
MITOTIC CYCLIN
G1 CYCLIN
G1
Start
S
G2
M
G1
Rb, P53, p16
CDK
S PHASE
CYCLIN
TYROSINE
PHOSPHORYLATION
MITOTIC CYCLIN
G1 CYCLIN
G0- quiescent
•
• Anaphase-promoting complex (APC)
– triggers the events leading to destruction of
the cohesins thus allowing the sister
chromatids to separate;
– degrades the mitotic cyclin B promoting exit
from mitosis
Check points & mechanism of DNA repair:
Cell has several systems to interrupt the
cell cycle if something goes wrong.
(i) DNA damage checkpoints. These sense DNA damage.
-
G1 checkpoint: Damage to DNA inhibits the action
of CDK thus stopping the progression of the cell
cycle until the damage can be repaired
Checkpoints & mechanism of DNA repair
- The common repairing mechanisms are
mismatch repair, base excision repair, nucleotide
excision repair, double strand break repair
- If the damage is so severe that it cannot be repaired,
the cell self-destructs by apoptosis.
(ii) Check point for successful replication of DNA
is present at S phase
Checkpoints & mechanism of DNA repair
(iii) Spindle checkpoints.
– detect any failure of spindle fibers that attach to
kinetochores and arrest the cell in metaphase until
all the kinetochores are attached correctly
(M
checkpoint )
– detect improper alignment of the spindle itself and
block cytokinesis
– trigger apoptosis if the damage is irreparable.
Cancer and Oncogenes
• All the checkpoints examined require the
services of a complex of proteins.
• Mutations in the genes encoding some of these
have been associated with cancer: oncogenes
• Checkpoint failures allow the cell to
continuously divide despite damage to its
integrity?? “developing cancer”
Growth Factors and Cancer
• Two main genes
– Tumor-suppressor Genes
– Proto-oncogenes.
Proto-oncogenes.
• PDGF and many other growth factors, stimulate cell division by
triggering G1 checkpoint by aiding the formation of cyclins
• Genes that normally stimulate cell division are sometimes called
proto-oncogenes because mutations that cause them to be
overexpressed or hyperactive convert them into oncogenes (Greek
onco, “cancer”).
•
Even a single mutation (creating a heterozygote) can lead to cancer
if the other cancer preventing genes are non-functional.
– E.g. myc, fos, and jun,
Tumour-suppressor Genes
• They block passage through the G1 checkpoint by
preventing cyclins from binding to Cdk, thus inhibiting
cell division.
• When mutated, they can also lead to unrestrained cell
division, but only if both copies of the gene are mutant.
• Hence, these cancer-causing mutations are recessive.
• Rate of cancer cell growth:
The proportion of cancer cells growing and making new
cells varies. If more than 6 -10% of the cells are making
new cells, the rate of growth is considered
unfavourably high.
• S-phase fraction and Ki-67 tests may be required to
measure rates of cell growth but treatment decisions are
made on other more reliable cancer characteristics.
• "Grade" of cancer cell growth: Patterns of cell growth are rated on
a scale from 1 to 3 (also referred to as low, medium, and high
instead of 1, 2 or 3).
– Calm, well-organized growth with few cells reproducing is considered
grade 1. Disorganized, irregular growth patterns in which many cells
are in the process of making new cells is called grade 3. The lower the
grade, the more favourable the expected outcome.
• Dead cells within the tumour: necrosis (or dead tumour cells) is
one of several signs of excessive tumour growth. It means that a
tumour is growing so fast that some tumour cells die.
Cell growth disorders
• A series of growth disorders can occur at the cellular level and
these underpins much of the subsequent course in cancer,
– group of cells display uncontrolled growth and division
beyond the normal limits,
– invasion (intrusion on and destruction of adjacent tissues),
– metastasis (spread to other locations in the body via lymph or
blood).
LABILE CELL
– cells that multiply constantly throughout life. They spend little
or no time in the quiescent G0 phase of the cell cycle, but
regularly performs cell division .
– E.g. skin cells, cells in the gastrointestinal tract and blood cells
in the bone marrow.
– It is mainly not the segments of the cell cycle that go faster (i.e.,
but rather a short or absent G0 phase.
– higher risk of becoming malignant and develop cancer.
Note:
• Cytotoxic drugs inhibit the proliferation of dividing
cells, with the malignant cells as the desired target.
• This has adverse effect against the cells normally
dividing in the body, and thus impairing normal
body function of skin, GI tract and bone marrow.
Positive Growth Regulators:
Promoting Cell Division
• Rous discovered that he could grind up sarcomas and
extract an unidentified substance that, when injected into
healthy chickens, caused cancer.
– not bacteria because it was carefully filtered,
• so something much smaller that could pass through the
filter.
– first animal tumor virus, which was named the Rous sarcoma
virus in honour of its discovery and the type of tumor from
which it was obtained.
Negative Growth Regulators:
Inhibiting Cell Division
• For a cell to divide, proto-oncogenes
must be activated to promote the
process, and tumor suppressor genes
must be inactivated to allow the
process to happen.
Example
p53
• This is known as tumour suppressor gene
• The p53 protein senses DNA damage and can halt
progression of the cell cycle in G1 (by blocking the
activity of CDK2).
• If both copies (as mutations in p53 are recessive) of the
p53 gene is mutated the above mechanism fails
• The p53 protein is also a key player in apoptosis,
forcing "bad" cells to commit suicide.
p53
Note :
• More than half of all human cancers do, in fact,
harbor p53 mutations and have non functioning
p53 protein.
Note:
• Inappropriate division of a clone of cells at the
inappropriate time lead to hypertrophy/ hyperplasia/
neoplasia
• Cell cycle is controlled by Genes, which secretes growth
and inhibitory stimuli with contact inhibition (cell to
cell)
• Any errors in the entry or exit in the cell cycle could
cause a tumour
Control at different
stages of the cell cycle
G0Phase
• A cell may leave the cell cycle,
temporarily or permanently.
i.e. it exits the cycle at G1 and enters a
stage designated G0
• G0 cell is often called "quiescent“-not
proliferating.
• Many G0 cells are in resting stage and
does not divide; but they carry out their
functions in the organism.
e.g. secretion, attacking pathogens.
• G0 to G1 requires growth factor
G0Phase
• If G0 cells are terminally differentiated: they will never
reenter the cell cycle but instead will carry out their
function in the organism until they die.
e.g. Terminally differentiated neurons cannot undergo
cell-cycle re-entry.
Note: Epithelial cells divide more than twice a day,
Liver cells divide only once every year or two,
spending most of their time in G0 phase
• Most of the lymphocytes in human blood
are in G0.
However, with proper stimulation, such
as encountering the appropriate antigen,
they can be stimulated to reenter the cell
cycle and proceed on to new cycle.
G0Phase
• G0 represents not simply the absence of signals
for mitosis but an active repression of the
genes needed for mitosis.
• Cancer cells cannot enter G0 and are destined
to repeat the cell cycle indefinitely.
Note: Normal cell exist in G0 more than cancer
cells
Sexual reproduction
•
Notice that when meiosis starts, the two copies of sister chromatids
number 2 are adjacent to each other. During this time, there can be
genetic recombination events. Parts of the chromosome 2 DNA gained
from one parent will swap over to the chromosome 2 DNA molecule that
received from the other parent
•
It is these new combinations of parts of chromosomes that provide the
major advantage for sexually reproducing organisms by allowing for new
combinations of genes and more efficient evolution.
Specialization & Communication of Cells
• Larger the organism, the greater the need for different types
of cells with different structures and functions.
• Specialized types of cells that are especially suited to
specific duties ensures that all the processes necessary for
the life of the organism are carried out quickly and
efficiently.
• Specialized cells fulfil a wide variety of needs in
multicellular organisms.
• Secondly principle that applies to all
multicellular organisms is that of cell
communication.
• With the diversity of cells & tissues found in
a multicellular organism, they must have
some way to coordinate their activities, and
must be able to communicate with one
another.
Cell – cell Interactions
• Cell-cell commu-nication allows an individual cell to
determine its position in the body, to adjust its
metabolism to suit its particular func-tion, and to
grow and divide at the proper time, in concert with
its neighbours
• Cells must be ready to respond to essential signals in
their environment by releasing small signalling
molecules, which are received by target cells.
Ligand-Receptor Interactions
• Molecules that activate (or, in some cases,
inhibit) receptors :
– hormones
– neurotransmitters
– cytokines
– growth factors but all of these are called
receptor ligands
Types of Signalling
• distant locations in a multicellular organism e.g. endocrine
signalling by hormones;
• nearby cells
e.g. paracrine stimulation by cytokines;
• secreted by themselves ( = autocrine stimulation)
• also respond to molecules on the surface of adjacent cells
e.g. producing contact inhibition
• Some cell-to-cell communication requires direct cell-cell contact.
• Some cells can form gap junctions that connect their cytoplasm to
the cytoplasm of adjacent cells.
– E.g. gap junctions between adjacent cells allows for action potential
propagation from the cardiac pacemaker region of the heart to spread
and co-ordinately cause contraction of the heart.
• Notch signalling mechanism -juxtacrine signalling (also known as
contact dependent signalling) in which two adjacent cells must
make physical contact in order to communicate.
Synaptic Signalling
• Neurons communicate with distant cells but they are not
carried to the responding cells by the circula-tory
system.
• The site at which the neurotransmitters are released is
called a chemical synapse. While paracrine signals cross
interstitial fluid between cells, neurotransmitters cross
the synapse and persist only.
• Adjacent cells can signal others by direct contact, while
nearby cells that are not touching can communi-cate by the
release of paracrine signals. Two sys-tems mediate
communica-tion over much longer dis-tances: the endocrine
system releases hormones that are carried by circulating
body fluids to distant cells; in ani-mals, the nervous system
se-cretes neurotransmitters from long cellular extensions
that end close to the re-sponding cells.
• Signalling molecules may trigger: an immediate change in
the metabolism of the cell (e.g., increased glycogenolysis
when a liver cell detects adrenaline);
• an immediate change in the electrical charge across the
plasma membrane (e.g., the source of action potentials);
• a change in the gene expression — transcription — within
the nucleus. (These responses take more time.)
Pathways by which a Chemical Signal
Turns on Gene Expression
• Two categories of signalling molecules
(i) steroids and nitric oxide diffuse into the cell & bind
internal receptors.
(ii) Proteins & peptides bind to receptors displayed at the
surface of the cell.
– These are transmembrane proteins: extracellular
portion binds the ligand & intracellular portion activates
proteins in the cytosol that eventually regulate gene
transcription in the nucleus.
Receptors
• When a signalling molecule reaches a
target cell, cell have a specific means of
receiving it and acting on its message.
• This responsibility is carried out by a
class of proteins called receptors.
• Cell surface receptors are glycoproteins that are
embedded or otherwise attached to the cell's
plasma membrane and have a binding site for
specific ligands (cytokines, hormones, growth
factors, neurotransmitters, adhesion molecules,
etc.), exposed to the extracellular environment.
• Ligand binding to a cell surface receptor generally
leads to a biological signal
Protein binding diagram
• The steroid–receptor complex acts on
specific genes, activating the production
of the proteins they encode
e.g. genes that are activated by progesterone
in target cells in the uterus, for example,
encode proteins that are necessary for the
proper growth of the uterine lining.
• How does nitric oxide serve as a signal to lower blood
pressure?
• State five molecules that act intra-cellularly to alter
gene expression
Cortisol, oestrogen, progesterone, vitamin D &
thyroid hor-mone
• State five molecules that act on the surface receptors.
Insulin, glucagon, GH, adrenalin, PDGF
• How Cell Surface Receptors Initiate Changes
inside the Cell
• specific chemical reactions are triggered inside a
cell by an external signal, causing a series of
protein activations known as a signal cascadesignal transduction.
• Cell surface receptors transduce ligand signals by a variety
of mechanisms such as receptor clustering, activation of a
hidden enzymatic activity, opening of ion channels, etc
1. Cell surface receptors trigger signal cascades by binding
external signalling molecules, changing shape, and then
activating or inactivating specific proteins inside the cell.
e.g. G proteins and enzyme-catalyzed phosphorylation or
specific nucleotides such as GTP.
2.
biological signal that is propagated towards the cell
interior, result in
proliferation, differentiation, apoptosis, degranulation, etc.
Cell surface receptors
•
Chemically gated ion channels are multipass transmembrane proteins
that form a pore in the cell mem-brane. This pore is opened or closed by
chemical signals.
•
Enzymic receptors are single-pass transmembrane proteins that bind the
signal on the extracellular surface and contain a catalytic region on their
cytoplasmic portion that initiates enzymatic activity inside the cell.
•
G protein-linked receptors bind to the signal outside the cell and to G
proteins inside the cell. (~ The G protein-linked receptor is a seven-pass
transmembrane protein.
•
Chemically Gated Ion Channels
• Integral protein has a pore that con-nects
the extracellular fluid with the cytoplasm
where ions pass through it, so the protein
func-tions as an ion channel.
• Ion chan-nels open or close when
neurotransmitter molecules bind to the
protein.
Enzyme Receptors
• Binding of a signal molecule to the receptor activates
the enzyme. In almost all cases, these enzymes are
protein kinases, that add phosphate groups.
• Each receptor is a single-pass transmembrane protein
(the amino acid chain passes through the plasma
membrane only once); the portion that binds to the
signal molecule is outside the cell, and the por-tion
that carries out the enzyme activity is exposed to the
cytoplasm.
G Protein-linked Receptors
• Receptors in this category are members of the largest
superfamily of surface receptors. Each is a seven-pass trans-
membrane protein
• signal molecule binds the receptor protein changes shape,
causing the associated G protein to bind GTP and become
activated.
• The activated G protein then diffuses away from the
recep-tor, starting a chain of events that ultimately brings
about the response of the cell.
G Protein-linked Receptors
How Cell Surface Receptors Initiate Changes inside
the Cell
• Cell response to an external signal is known as signal
transduction.
• The signal is transferred, or transduced, from the outside to
the inside of the cell.
• It triggers a series of chemical reactions that activate
proteins inside the cell-referred to as a signal cascade.
• Each type of signalling molecule binds to a specific type of
receptor on the cell surface, causing a specific signal
cascade that activates specific proteins.
G proteins
• Bind to and are regulated by nucleotides
with a guanine base:
• When a G protein is bound to GDP, it is
inactive. When an inactive G protein binds
to an activated receptor, however, it is able
to release GDP and bind GTP from the
cytosol.
G-Protein-Coupled Receptors (GPCRs)
• Many ligands that alter gene expression by
binding GPCRs:
– protein and peptide hormones
e.g. TSH, ACTH.
– Serotonin and GABA (which affect gene
expression in addition to their role as
neurotransmitters)
Turning GPCRs Off
• A cell must also be able to stop responding to a signal. Several
mechanisms cooperate in turning GPCRs off. When activated, the
Gα subunit of the G protein swaps GDP for GTP. However, the Gα
subunit is a GTPase and quickly converts GTP back to GDP
restoring the inactive state of the receptor. The receptor itself is
phosphorylated by a kinase, which not only reduces the ability of
the receptor to respond to its ligand but recruits a protein; β-
arrestin, which further desensitizes the receptor, and triggers the
breakdown of the second messengers of the GPCRs: cAMP for
some GPCRs, DAG for others.
G protein diagram
Cytokine Receptors
• Most of these fall into one or the other of two major families:
1. Receptor Tyrosine Kinases (RTKs) and
2. Receptors that trigger a JAK-STAT pathway.
• Receptor Tyrosine Kinases (RTKs)
The receptors are transmembrane proteins that span the plasma
membrane just once.
• Some ligands that trigger RTKs:
e.g. Insulin, Vascular Endothelial Growth Factor , PDGF,EGF, FGF, M-CSF
Amplifying and Combining Signals
inside the Cell
• The activation of many proteins at each step of a
signal cascade greatly amplifies the original signal.
Signal cascades that modify existing proteins inside
the cell occur in a matter of seconds; those that
activate genes to produce new proteins can take
several hours. Certain proteins can participate in
multiple signal cascades, allowing the cell to
integrate different external signals.
Defeating Deadly Bacterial Toxins
• Knowing how signal cascades are affected
by deadly bacterial toxins will allow
biologists to design drug therapies that
specifically block their effects.
Signal Transducers
Signal Amplification & Adhering Cell
• Both enzyme-linked and G protein-linked receptors receive
signals at the surface of the cell
• signals are relayed to the cytoplasm or the nucleus by
second messengers, which influence the activity of one or
more enzymes or genes and so alter the behavior of the cell.
• They uses a chain of other protein messengers to amplify
the sig-nal as it is being relayed to the nucleus.
Amplifying & Combining Signals
inside the Cell
• Imagine a situation in which a single hormone or
growth factor binds to a cell surface receptor. If this
binding event resulted in the activation or
phosphorylation of only one protein inside the cell,
many binding events at the cell surface would be
needed in order to bring about any significant
change in the cell. To avoid such an inefficient
arrangement, most signal cascades greatly amplify
the initial signal. A signal cascade is like a huge
avalanche on a snow-covered mountain that is
started by one small icicle falling off a tree at the top
of the slope.
•
Communicating Cell Junctions
• cell recognition proteins allow specific kinds
of cells to bind to each other to make direct
physical contact called cell junction.
• three types of cell junctions
– tight junctions
– desmosomes
– gap junctions
•
•
•
•
•
•
•
Cell junctions can be classified into three functional groups:
1. Occluding junctions seal cells together in an epithelium in a way that
prevents even small molecules from leaking from one side of the sheet to the
other.
E.g. tight junctions (vertebrates only) & septate junctions (invertebrates
mainly)
2. Anchoring junctions mechanically attach cells (and their cytoskeletons) to
their neighbors or to the extracellular matrix.
E.g cell-cell junctions (adherens junctions)
cell-matrix junctions (focal adhesions)
3. Communicating junctions mediate the passage of chemical or electrical
signals from one interacting cell to its partner.
The major kinds of intercellular junctions within each group are listed in Table
16.1. We discuss each of them in turn, except for chemical synapses, which are
formed exclusively by nerve cells and are considered in other course unit.
gap junctions, chemical synapses, plasmodesmata (plants only)
Cell recognition and adhesion involve
proteins at the cell surface
• Membrane glycoprotein (80% sugar) that is partly
embedded in the plasm is responsible for cell recognition.
• protein has specific chemical groups exposed on its
surface where they can interact with other substances,
including other proteins.
• Two types.
(i) homotypic: The same molecule sticks out of both
cells,
& exposed surfaces bind to each
other.
(ii)heterotypic: binding of cells with different
proteins.
e.g. Male and female cells recognize each other
Gap Junctions
• Allow small molecules to pass directly from Cell to Cell
• In EM appears as 2 adjacent cells separated by a narrow gap (2–4 nm)
• The gap is spanned by channel-forming proteins (connexins) to form
(connexons)
• allow inorganic ions and other small water-soluble molecules to pass
directly from the cytoplasm of one cell to the other,
• couple the cells both electrically and metabolically to share small
molecules. But not macromolecules (e.g proteins, NA)
Function of gap junctions
• In nerve cells - electrically coupled, allowing action
potentials to spread rapidly from cell to cell, without the
delay that occurs at chemical synapses.
e.g when speed and reliability are crucial-in certain escape
responses in fish and insects.
• Synchronizes the contractions
– heart muscle cells in heart
– smooth muscle cells involved in the peristaltic movements of the
intestine.
• Gap junctions also occur in tissues that do not contain
electrically excitable cells.
– e.g. Release of noradrenaline from sympathetic nerve endings in
response to a fall in blood glucose levels stimulates hepatocytes
to increase glycogen breakdown and release glucose into the
blood.
• Note: Not all the hepatocytes are innervated by
sympathetic nerves, when glucose level fall, however by
means of the gap junctions that connect hepatocytes, the
signal is transmitted .
• The normal development of ovarian follicles
also depends on gap-junction-mediated.
• Cell coupling via gap junctions also seems to be
important in embryogenesis.
Permeability of Gap Junctions Can Be Regulated
• Like ion channels, individual gap-junction channels do not
remain continuously open; instead, they flip between open
and closed states.
• The permeability of gap junctions is rapid (within seconds)
and reversibly reduced by decrease cytosolic pH (not
known) / increase cytosolic [free Ca2+ ] to very high levels.
• They are dynamic structures that can undergo a reversible
conformational change that closes the channel in response
to changes in the cell.
• Purpose of Ca2+ control: when a cell is damaged, its
plasma membrane become leaky, fluid, such as Ca2+
and Na+, and then move into the cell, and valuable
metabolites leak out.
• If the cell were to remain coupled to its healthy
neighbours, the large influx of Ca2+ into the damaged
cell causes its gap-junction channels to close
immediately, effectively isolating the cell and
preventing the damage from spreading to other cells.
• Gap-junction communication can also be regulated by
extracellular signals.
E.g. neurotransmitter dopamine, for example, reduces gapjunction communication between a class of neurons in the
retina in response to an increase in light intensity. This
reduction in gap-junction permeability helps the retina
switch from using rod photoreceptors, which are good
detectors of low light, to cone photoreceptors, which detect
color and fine detail in bright light.