Lecture 8 Flashcards
cWhat is the cytoskeleton?
A network of intracellular fibers that maintain the shape of a cell providing structural
strength, resistance to mechanical stress, and resilience to deformation. It also plays a role
in intracellular transport, and cell motility.
What three fibers are in the cytoskeleton
- microfilaments
-intermediate filaments
-microtubules
What is the function of Microfilaments
Cell shape, motility, endo- and exocytosis,
secretion and vesicle transport
What are microfilaments composed of
G-actin
‣ Have binding site for ATP or ADP that
play a role in polymerization
‣ Highly conservative and ubiquitous
expression
-Polymerize with F actin
What are 4 special feature of microfilaments
✓ Very dynamic structures that can polymerize and
depolymerize rapidly within the cell
✓ Form a mesh below the plasma membrane.
✓ They link with proteins embedded in the membrane,
connecting with the ECM.
✓ The formation, growth, and dissolution of
microfilaments is strictly regulated by more than 100
proteins
______________-: affect normal actin polymerization/ depolymerization
results in changing the shape of any cells, inhibiting cell motility, and preventing the outgrowth of axons from ganglion
Fungal metabolites Cytochalasin
B and Phalloidin
What is the function of Intermediate filaments
Structural role, providing support to the nucleus
and the plasma membrane
✓ Form the most stable element of the cytoskeleton
What is the structure of an intermediate filament
strong, highly flexible fibers that provide mechanical support
______________: Cause: Rare, autosomal recessive mutation in the LMNA
gene, which results in the production of an abnormal lamin
A protein called progerin (a farnesylated form of prelamin
A, which is retained due to the mutation). Accumulation of
progerin destabilizes nuclei, altering their shape
predisposing patients to manifest signs of premature aging.
Clinical presentation: children are born looking normal and
begin to develop clinical signs of disease during year one.
Physical appearance and clinical findings change
dramatically each year they age. Life expectancy is 5-20
years. Children usually develop premature progressive
atherosclerosis and die of heart failure
Hutchinson Gilford disease
What is the treatment for hutchinson Gilford disease
oral farnesylation inhibitor that prevents the accumulation of progeria and protein like proteins resulting in restoration of nuclear morphology and extending patient lives
Intermediate filament disease can also result in ______________
skin diseases due to mutations in gene coding various keratins
_____________________
The defect in most common types of EBS
is in keratin 5 or 14, which makes up
intermediate filaments of the basal
keratinocytes leading to cytolysis of the
basal cells and blisters.
Epidermolysis Bullosa Simplex (EBS)
_______________________
Mutations in the keratin 1 and keratin 9
genes. Skin disorder characterized
clinically by diffuse, yellow thickening of
the skin of the palms and soles
Epidermolytic Palmoplantar
Keratoderma (EPPK)
What are the functions of microtubules
mitotic spindle formation and
function, intracellular movement of endocytic and exocytic vesicles
Structural components of cilia and flagella.
Maintain the structure of axons and dendrites as well as participate in the axoplasmic flow of material along neuronal
processes.
What are microtubules composed of
13 logitiudaly arranged protofilaments
Each protofilament is comprised of
globular α-tubulin and β-tubulin
_____________________
Mutations in genes affecting the synthesis of dynein, a cytosolic MAP that power ciliary and flagellar
movements.
Results in:
‣ male sterility due to immobile spermatozoa
‣ situs inversus (a mirror image of chest and abdominal organs compared to normal human anatomy) due to
lack of proper cell movement during embryogenesis
‣ chronic respiratory infections due to dysfunctional nasal cilia.
Kartagener syndrome
_____________
‣Anti-cancer drugs: vinblastine and paclitaxel
‣Acute gouty arthritis: colchicine
‣Anti-fungal: griseofulvin
Pharmacological treatments that disrupt the microtubule
assembly or disassembly
The most abundant protein in
the human body
✓ Very long lived (10 years)
✓ Ubiquitously present in
different organs and systems
Collagen
What is the structure of collagen
fibrous protein compose of 3 alpha chains filing a triple strange rope like structure
The structure is stabilized by interchain H bonds
Different chains have different collagen fibers
What amino acids are prevalent in collagen
glycine and proline
______________________
Greatly decreased tensile strength of the
assembled collagen fibers due to lack of H-bond
formation
‣Easy bruising
‣Loose teeth and bleeding gums
‣Poor wound healing
‣Poor bone development
Vitamin C diffecieny Scurvey
______________ is a copper containing extracellular enzyme that oxidatively dominates some of the lysine and hydrolysine residues forming reactive aldehydes. They form covalent cross links in the mature collagen fibers
Lysyl oxidase
_______________________:
Copper deficiency: mutations in the ATP7A gene (PM
Cu2+ transporter) leading to lack of Cu2+
‣ X-linked recessive (~30% of MNK are due to new
mutations and 70% are inherited)
‣ Symptoms: weak muscle tone (hypotonia), sagging
facial features, seizures, intellectual disability, and
developmental delay. The patients have brittle hair
(kinky hair disease)
Menkes Syndrome
_________ copper overload
Wilson’s disease
