Signaling Mechanisms, Cellular
Adhesion, and More diseases
Genetics
Signal Transduction
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Occurs on the cell membrane on both
side
Cells n a multicellular organism need
to communicate with other cells
In signal transduction molecules on
the cell membane, assist,
transmit,and amplify messages.
Transduction means to change the
signal from the environment into a
common message understood by the
cell.
Signal transduction

The transduction occurs
between a receptor on the
outside of the cell and a
molecule in the cytoplasm
which will amplify the signal
so that it is received and
acted on
First messengers
Messages received by
receptors on the outside
 These are the first
messengers – the signal can
be light, a chemical
gradient,temperature,
toxins, hormones, or growth
factors

Receptor
A molecule which is the
signal binds to the
receptor.
 The receptor is attached to
a transmembrane protein(
spans the cell membrane)
 The signal causes a change
in the shape or
conformation of the
transmembrane protein

Cytoplasmic responses
The membrane affects a
regulator molecule that
then activates an enzyme
 The enzyme causes ATP to
form CAMP( cyclic AMP)
 This is a generalized
message that can be
transmitted to the nucleus
or to other molecules in the
cell

Growth Factor
NF1
Effects of
Neurofibromatosus
NF1 and Growth
factors
Chromosome 17
 Neurofibromatosis is an
autosomal dominant disorder
characterized particularly by
cafe-au-lait spots and
fibromatous tumors of the skin.
Other features are variably
present
 Caused by a mutation in the
gene for neurofibromin

NF1 and cancer

Neurofibromatosis is an
autosomal dominant
disorder characterized
particularly by cafe-au-lait
spots and fibromatous
tumors of the skin. Other
features are variably
present
Protein
The protein has been called
neurofibromin 1; 2839
amino acids
 Expression is tissue and
development stage specific
 Function GTPase activating
protein
 (GAP) interacting with
p21RAS -> tumor
suppressor.

Chromosome 17
Cellular Adhesion
Cells touch each other
through adhesion
 A precise set of
interactions between
proteins joins the cells in
tissues

Cellular Adhesion
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Inflammation – the painful,red
swelling at a site of injury or
infection- illustrates cell adhesion
Inflammation is caused by white
blood cells. White blood cells flood
to injured areas to prevent infection
Cellular adhesion molecules help
guide white blood cells to the injured
area( genetically controlled)
Three Types of CAMS –
cellular adhesion
molecules
Selectins provide traction by
coating the white blood cells to
slow them
 Blood cells release chemical
attractants that signal white
blood cells to stop this
activatesCAMs called integrins
that latch onto white blood
cells and CAMs called adhesions
receptor proteins

Adhesion receptor
This extends from the
capillary wall at the injury
site and touches the
cytoskeleton beneath the
capillary lining
 The integin and receptor
protein bind the WBC and
pull in through the
membrane to the injury site

Failure to work
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Creates a disease
Called leukocyte adhesion
deficiency
A deficiency of CAMS
The blood does not stop at
injured places
Lack of cell adhesion allows
cells to travel through the body
and metasticize
Deficiency of CAMs

Can also lead to arthritic
situations where WBC
attach to a joint when
there is not injury
WBC
Mechanism
LAD

LAD is a rare PI disease, found
in one out of every million
people. This disease causes
recurrent, life-threatening
infections. Phagocytes cannot
find their way to the site of
infection to fight off invading
germs. LAD is autosomal
recessive disease, meaning that
to be born with this disease,
both parents must have the
affected gene.
Cause

LAD is caused by a lack of beta
2 integrin, also called CD18,
molecules. These molecules are
normally found on the outer
surface of phagocytes. Without
them, the phagocytes cannot
attach to blood vessel walls and
enter infected tissues where
they help fight infection.
Mutations in the gene that
instructs, or codes for, the
production of CD18 cause LAD.
Infections and LAD
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Children with LAD cannot fight off
infection properly. They may have
Severe infections of the soft tissue
Eroding skin sores without pus
Severe infections of the gums with
tooth loss
Infections of the gastrointestinal
tract
Wounds that heal slowly and may
leave scars
Lesch- Nyhan

Lesch-Nyhan syndrome (LNS) is
a rare, inherited disorder
caused by a deficiency of the
enzyme hypoxanthine-guanine
phosphoribosyltransferase
(HPRT). LNS is an X-linked
recessive disease-- the gene is
carried by the mother and
passed on to her son. LNS is
present at birth in baby boys.
HPRT

The lack of HPRT causes a
build-up of uric acid in all body
fluids, and leads to symptoms
such as severe gout, poor
muscle control, and moderate
retardation, which appear in
the first year of life. A
striking feature of LNS is selfmutilating behaviors –
characterized by lip and finger
biting – that begin in the
second year of life.
Uric acid

Abnormally high uric acid
levels can cause sodium
urate crystals to form in
the joints, kidneys, central
nervous system, and other
tissues of the body, leading
to gout-like swelling in the
joints and severe kidney
problems.
Symptoms

Neurological symptoms include
facial grimacing, involuntary
writhing, and repetitive
movements of the arms and legs
similar to those seen in
Huntington’s disease. Because a
lack of HPRT causes the body
to poorly utilize vitamin B12,
some boys may develop a rare
disorder called megaloblastic
anemia.
MSUD – Maple Syrup
Urine Disease

Maple Syrup Urine Disease (MSUD)
or branched-chain ketoaciduria is
caused by a deficiency in activity of
the branched-chain a-ketoacid
dehydrogenase (BCKD) complex (1,
2). This metabolic block results in
the accumulation of the branchedchain amino acids (BCAAs) leucine,
isoleucine, and valine and the
corresponding branched-chain alphaketo acids (BCKAs).
Branched Amino acids
Characteristics

MSUD is an autosomal recessive
metabolic disorder of panethnic
distribution. The worldwide
frequency based on routine screening
data from 26.8 million newborns is
approximately one in 185,000. In the
inbred Old Order Mennonite
population of Lancaster and Lebanon
Counties, Pennsylvanis, MSUD occurs
in approximately one in 176
newborns.
Protein

The human BCKD complex
affected in MSUD is a
macromolecular metabolic
machine (molecular mass 4
x 106 daltons) loosely
associated with the inner
membrane of the
mitochondria.
Affected Pathway
Dietary
recommendations
MSUD- Synthetic Diet
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The diet centers around a synthetic
formula or "medical food" which
provides nutrients and all the amino
acids except leucine, isoleucine and
valine. These three amino acids are
added to the diet with carefully
controlled amounts of food to
provide the protein necessary for
normal growth and development
without exceeding the level of
tolerance.
Wilson’s Disease

Wilson's disease causes the
body to retain copper. The
liver of a person who has
Wilson's disease does not
release copper into bile as
it should.
Symptoms

Wilson's disease is hereditary.
Symptoms usually appear
between the ages of 6 and 20
years, but can begin as late as
age 40. The most characteristic
sign is the Kayser-Fleischer
ring—a rusty brown ring around
the cornea of the eye that can
be seen only through an eye
exam.
Liver and Spleen
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Other signs depend on
whether the damage occurs
in the liver, blood, central
nervous system, urinary
system, or musculoskeletal
system. Many signs can be
detected only by a doctor,
like swelling of the liver and
spleen
Other symptoms

Some symptoms are more
obvious, like jaundice, which
appears as yellowing of the
eyes and skin; vomiting
blood; speech and language
problems; tremors in the
arms and hands; and rigid
muscles.
Treatment

The disease is treated with
lifelong use of Dpenicillamine or trientine
hydrochloride, drugs that
help remove copper from
tissue, or zinc acetate,
which stops the intestines
from absorbing copper and
promotes copper excretion
Dietary Restrictions
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Patients will also need to
take vitamin B6 and follow a
low-copper diet, which
means avoiding mushrooms,
nuts, chocolate, dried fruit,
liver, and shellfish.
Epidermolysis bullosa

Epidermolysis bullosa (EB) is a
group of inherited bullous
disorders characterized by
blister formation in response to
mechanical trauma. Historically,
EB subtypes have been
classified according to skin
morphology.
Types

EB is classified into 3 major
categories, including (1) EB
simplex (EBS; intraepidermal
skin separation), (2) junctional
EB (JEB; skin separation in
lamina lucida or central BMZ),
and (3) dystrophic EB (DEB;
sublamina densa BMZ
separation; see
Examples
Biotinidase deficiency

Biotinidase is a ubiquitous
mammalian cell enzyme
occurring at high levels in the
liver, serum, and kidney. The
primary function is to cleave
biotin from biocytin, preserving
the pool of biotin for use as a
cofactor for biotin dependent
enzymes, namely the 4 human
carboxylases

Disease caused by complete or
partial absence of the enzyme is
associated with a wide spectrum of
clinical manifestations, including
abnormalities of the neurological,
dermatological, immunological, and
ophthalmological systems. In spite of
its rarity, early recognition is crucial
because expeditious treatment may
reverse all of its manifestations
Treatment

If treated promptly,
biotinidase deficiency may be
asymptomatic. Prolonged
symptoms prior to institution of
biotin therapy may leave the
patient with varying degrees of
neurological sequelae, including
mental retardation, seizures,
and coma. Death may result
from untreated profound
biotinidase deficiency.
Neurological Problems
Developmental delay
 Ataxia
 Neuropathy
 Auditory nerve dysfunction
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Immunological Problems
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Chronic and possibly lethal fungal
infections characterize
immunological deficiencies.
Cellular immunity abnormalities
are possibly due to accumulation
of toxic metabolites or biotin
deficiency itself.
The immunological dysfunction is
ameliorated with biotin treatment.