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Home Page Flashcards Cytoskel,Adhesions/Junct,Coll/ - Flashcards

Cytoskel,Adhesions/Junct,Coll/ – Flashcards

Deloris Connelly
7 July 2022

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question
What are the 3 major types of protein filaments that form the cytoskeleton?
answer
  1. actin filament (5-9 nm)
  2. intermediate filament (10 nm)
  3. microtubule (25nm)
accessory proteins (AP): essential for controlled assembly of cytoskeleton
 
motor proteins (type of AP): essential for movement of organelles or filaments
 
question
function of cytoskeleton?
answer
  • stabilizes components in cytosol
  • external shape
  • internal and external movement
**remember, it is a highly DYNAMIC structure; actin and microtubules reorganize rapidly during mitosis, ie**
question
where are each of the filaments located within the cell?
answer
ACTIN: mostly beneath the plasma membrane; cell surface organization
 
MICROTUBULES: long, rigid, hollow cylinders; one end attached to MTOC (centrosome or basal body) at center of cell; function as cell highways
 
INTERMEDIATE FILAMENTS: heterogenous family of rope-like fibers that span the entire cytoplasm from one cell-cell junction to another; tissue stability (IF anchoring junctions); form the nuclear lamina.
question
what are the classes of microtubules?
answer
  • LABILE: temporary, according to need;dispersed throughout cytoplasm
  • STABLE: form permanent parts of cell, including centrioles, cilia, flagella
question
what are important structural features of the microtubule?
answer
  • microtubules = polymers of α & β TUBULIN
  • wall = 13 protofilaments
  • inherent polarity: + (dynamic) and - (inert) ends
    • inert end attached to MTOC
    • change/grow/shrink @ + end
  • GTP cap: causes microtubule to grow in linear fashion; when hydrolyzed, MT depolymerizes and shrinks
  • MAPs: microtubule associated proteins that stabilize polymerization
  • catastrophins: MT destabilization
question
Microtubule associated proteins (MAPs)
answer
involved in tubulin polymerization, leading to stabilization of microtubules; growth rate enhanced
 
longer, less dynamic MTs formed
 
formation of functionally differentiated cytoplasm is promoted, ie: in the axons of neurons
 
**catastrophins (kinesin 13): opposite effect of MAPS; destabilize MTs, leading to catastrophe! shorter, more dynamic MTs formed
question
components of stable microtubules
answer
  • microtubule organizing centers (MTOCs)
    1. centrosome- cell center MTOC
    2. basal bodies of cilia, flagella
  • axoneme
    • motile core of cilia, flagella
question
centrosome
answer
  • main MTOC, center of cell
    • (-) ends of MT embedded w/in centrosome
  • components:
    • 2 centrioles (right angles to e/ other)
    • 1 pericentriolar cloud/material (centrosome matrix) with γ tubulin ring complexes
      • pericentriolar material provides the initiation sites for MT polymerization (nucleation)
question
how do the locations of a, b, and γ tubulin differ in microtubulin?
answer
  • a, B tubulin are everywhere throughout MT
  • γ tubulin ONLY IN MTOC (centrosome)
question
AXONEME
answer
a core of longitudinally arranged microtubules present in cilia and flagella; also contain dyneins.
 
  • CILIA: 9 peripheral doublets + 2 central singlets
  • FLAGELLA: same as cilia
BASAL BODY:  a special centriole (MTOC) that gives rise to either cilium or flagellum; pattern= 9 peripheral triplets + 0 central
question
cytoplasmic dynein
answer
  • ATP-dependent motor protein involved in transport along a MT from (+) --> (-) end.
  •  vesicle trafficking and localization of the golgi (inward)
  • INWARD MOVEMENT, towards (-) END
 

question
immotile cilia syndrome
answer
genetic lack of dynein arms 
 
lack motion of cilia: beat-like, wave-like
 
**ciliary dynein (closely related to cytoplasmic variety) is responsible for movement of cilia and flagella; dynein arms form bridges between neigboring doublets** 
question
Kinesin
answer
  • microtubule binding motor protein that uses hydrolysis of ATP to move along it
  • moves TOWARDS (+) END
  • kinesin = outward movement
  • ER movement faciliated by kinesin
question
functions of microtubules?
answer
  • organize cell via CENTROSOME
  • mitotic spindle formation
  • highways for organelle transport (ER, golgi, etc)
  • cell MOTILITY (cilia, flagella)
question
key actin features...
answer
  • 2 stranded helical polymers made of G-actin; polymerized into F-actin
  • polarity
  • ATP binding
  • located primarily under plasma membrane
question
actin polarity
answer
  • actin elongation mediated by formins
  •  formin dimer forms on (+) end and directs motion in that direction
question
actin cross-linking proteins
answer
either allow or block entrance of myosin molecules:
 
  • fimbrin in the filopodia causes tight packing of actin and does not allow for the entrance of myosin II; "parallel bundle"
  • alpha-actinin in stress fibers creates loose packing that allows myosin II to enter bundle, creating "contractile bundle"
  • spectrin is found in cell cortex and creates a gel-like network
question
what actin cross linking proteins are associated with micovilli's structure?
answer
  • villin
  • myosin I
these 2 proteins' crosslinking accounts for microvilli's shape
question
zonula adherens
answer
actin filaments are crucial in the strong binding of tubes (ducts, etc)
;
as epithelial cells curve to form a tube, the actin filaments strengthen the binding to keep tube intact
;
;adhesion belts; associated with actin filaments
question
functions of actin filaments
answer
  • external shape (cortex)
  • muscle contraction (myosin II binding)
  • anchoring junctions (cell-cell; cell-matrix)
  • microvilli formation
  • cleavage furrow in dividing cells
  • motility, polarity
  • development of tubes (epithelial)
question
key features of intermediate filaments
answer
  • rope-like
  • NO POLARITY
  • NOT ATP or GTP DEPENDENT (but maintains dynamism via phosphorylation)
  • assembly along ENTIRE length, not just as ends
  • easily bent, but difficult to break
question
location and other key features of intermediate filaments
answer
  • integrate with MT and actin
  • anchoring junctions via:
    • DESMOSOMES (cell-cell)
    • HEMIDESMOSOMES (cell-matrix)
  • span cytoplasm from one junction to another, lending TISSUE STRENGTH
question
important classes of IFs
answer
  • keratins (epithelia)
  • vimentin (mesenchymal cells)
  • desmin (muscle cells)
  • glial fibrillary acidic protein (GFAP)- astrocytes
  • neurofilaments (neurons)
  • lamins (nuclear lamina)
question
what are classic functions of intermediate filaments?
answer
  • structural support against rupturing forces
  • nuclear lamina formation (via lamins)
  • immunologic markers for ID of cells and corresponding tumors
question
cholchicine
answer
  • a microtubule specific drug
  • ;
  • prevents polymerization
  • ;
  • gout treatment
colchicine
question
vinca alkaloids
answer
microtubule specific drug
;
prevents polymerization (prevents mitosis)
;
anti-cancer drug
question
acrylamide
answer
intermediate filament specific toxin
;
causes disassembly or rearrangement of IF
;
neurotoxin
question
epidermolysis bullosa simplex
answer
a genetic defect that affects cytoskeleton
;
causes blistering of the skin via a mutant keratin gene
;
skin very weak, epidermis not intact because of defective keratin filament network
question
the cytoskeleton can experience negative changes secondarily through injury. what are some of the ways?
answer
  • Lou Gehrig's disease (ALS)
    • abnormal accumulation of neurofilaments in neurons
  • Alzheimer's disease
    • ;tangles; of neurofilaments and associated proteins (abnormal aggregations)
  • Alcoholic liver disease
    • keratin filaments accumulate in liver cells; called HYALINE or MALLORY BODIES
  • HPV --> koilocytosis
    • collapse of keratin filaments w/in affected cells
question
what are the classes of cell junctions?
answer
  1. occluding: tight junctions
  2. anchoring
    1. actin filament association- cell/cell (adherens junctions); cell/matrix (focal adhesions)
    2. intermediate filament association- cell/cell (desmosomes); cell/matrix (hemidesmosomes)
  3. communicating (channel forming): gap junctions
question
claudin and occludin
answer
tight junction proteins located on the apical perimeter of 2 adjacent cells
 
each protein binds to same one on the other cell (claudin-claudin; occludin-occludin)
 
tight junctions restrict the mobility of membrane proteins and passage of molecules between cells.
question
zonula adherens/ adhesion belt
answer
adherens junction
 
cell-cell: actin filaments from one cell to another linked by CADHERIN DIMERS
 
actin filament,
question
focal contact/adhesion
answer
cell to matrix anchoring junctions that link actin in the cytoskeleton with proteins in the ecm (ie: fibronectin). 
 
not present in epithelial cells, but common in connective tissue cells (ie: fibroblasts, WBCs, muscle cells, etc)
 
transmembrane integrin proteins bind to a protein component of the ecm  (ie: collagen, fibronectin, laminin) while their intracellular domains bind indirectly to bundles of actin  via actin anchr proteins (ie: vinculin, paxillin, talin)
question
dystrophin
answer
  • in skeletal muscle in muscular dystrophy there is a problem with protein DYSTROPHIN
  •  normally links actin to ecm via a glycoprotein complex
  •  in MD, dystrophin is either missing, altered, or decreased
  •  affects locomotive ability of cells
question
structure of a desmosome
answer
intermediate filament cell-cell adhesion junction
 
cells joined by CADHERIN-FAMILY adhesion proteins (desmoglein; desmocollin)
 
 
question
pemphigus vulgaris
answer
autoantibodies against desmoglein
 
deposition of immuniglobulin along plasma membranes of epidermal keratinocytes, leads to severe blistering
 
 
question
hemidesmosomes
answer

transmembrane integrins attach cell to matrix

 

matrix components: collagen, laminin, etc

 

BOLLOUS PEMPHIGOID: antibody against hemidesmosome binds at dermoepidermal junction

 

non-acantholytic blistering

 

question
gap junction
answer
interacting plasma membranes that form a junction or channel between them with 2 connexons binding to form an open channel between adjacent cells
 
each connexon composed of 6 subunits
question
why are gap junctions important?
answer
  • facilitate metabolic and electrical coupling between cells
  • coordinate actvities in epithelia, smooth muscle, heart muscle
question
what effect does calcium have on gap junction permeability?
answer
 
SHUT: high calcium or low pH
 
OPEN: low calcium or high pH
 
*ovarian follicle: gap junction communication between oocyte and granulosa cells; if there is a mutation in the junction components, INFERTILITY*
question
components of extracellular matrix?
answer
  • polysaccharides +/- protein
    • GAGs
    • proteoglycans
    • glycoproteins
  • fibrous and adhesive proteins
    • collagen
    • elastin
    • fibronectin
    • laminin
question
what are the four main GAG groups and what are they most responsible for?
answer
  1. HYALURON: connective tissue
  2. CHONDROITIN & DERMATAN SULFATE: cartilage, skin (related to aging) 
  3. HEPARAN SULFATE: basal laminae, cell surfaces
  4. KERATAN SULFATE:  cornea, cartilage
question
proteoglycans
answer
except for hyaluron, ALL GAGs are attached to a core protein --> proteoglycan
 
form very large molecules shaped like a bottle brush
 
proteoglycans may attach to hyaluronic acid forming a giant aggregate
 
along with fibrous/adhesive ptoeins, proteoglycans form a highly organized ECM
question
collagen
answer
most abundant protein in ECM and overall (25% total protein mass)
 
main types:
1) fibrillar i, ii, iii, v, xi
2) fibril-associated ix, xii
3) non-fibrillar/ network forming iv (basal laminae), vii (anchoring fibrils)
question
network forming collagen (IV, VII)
answer
anchoring plaque (type IV collagen)
 
anchoring fibril (collagen type VII)
 
the non-staggered fibrils of collagen VII orignate in basal lamina and insert into anchoring plaques of type IV collagen
 
both help to form network at the main interface between epithelial cells and connective tissue
question
structural features of collagen
answer
  • fiber (LM detection)
  • fibril (EM detection)
  • molecule: tropocollagen
    • striations come from staggered arrangement
  • cross-banding pattern
  • rich in PROLINE and GLYCINE
question
collagen synthesis
answer
INTRACELLULAR and EXTRACELLULAR STEPS
 
CELLS DONT FORM COLLAGEN W/IN CELL BODY
 
COLLAGEN FORMING W/IN IS A SIGN OF PATHOLOGY
 
BASIC STEPS:
synthesis of a-prochain
hydroxylation of selected prolines and lysines
glycosylation of hydroxylysines
self-assembly of 3 pro-a chains
procollagen triple helix formation
---secretory vessel--> secretion out of cell
cleavage of  propeptides
self assembly into fibril
aggregation of fibrils into fiber
 
question
collagen-associated diseases
answer
  • scurvy (vit C def prevents proline hydroxylation)
  • mutations: I, II, III collagen leads to osteogenesis imperfecta, chondrodysplasia, ehlers danlos syndrome) BONE DISEASE
  • dermatitis herpetiformis: antibodies against anchoring fibrils (VII)--the same antibodies that react with gluten
    • celiac disease
question
dermatitis herpetiformis
answer
skin problems as well as GI ones are common in people with celiac disease because of the cross reaction of the anti-gluten antibodies with the anchoring fibrils
 
IgA: the antibody that reacts against gluten & VII
 
Blisters form from dermal papillary microabscesses
question
elastin
answer
integral part of connective tissue
 
appear more amorphous than collagen on EM
 
networks of elastin molecules can stretch and recoil like a rubber band; cross linking of basic molecule (tropoelastin)
 
rich in proline, glycine; NOT glycosylated and lacks hydroxylysine
 
elastin core covered by sheath of microfibrils (ie, fibrillin)
 
walls of aorta
 

 
 
question
diseases related to elastin
answer
  • marfan syndrome: fibrillin gene mutation
  • elastic tissue defects, including tendency of aorta to rupture
question
adhesive glycoproteins
answer
responsible for linking ECM components to each other and to cells
 
  • fibronectin
  • laminin
question
fibronectin
answer
  • large adhesive glycoprotein with lots of domains for binding of:
    • itself
    • collagen
    • fibrin
    • proteoglycans
    • cell surfaces via integrin
  • fibronectin receptor (an integrin) links ECM to cytoskeleton
  • also there is plasma fibronectin
question
laminin
answer
a cross shaped glycoprotein abundantly present in basal laminae (basement membrane)
 
integral component of basal lamina, along with nidogen, perlecan, type IV collagen, and integrin(coming from w/in cell)
 
all these proteins interact with selves and with each other
question
what is the difference between basal lamina and basal membrane?
answer
the terms are NOT synonymous
 
basal membrane = lamina + underlying collagen fibers
 
also, remember that the lamina has 2 layers:
LAMINA RARA &
LAMINA DENSA
question
functions of basal laminae
answer
basal lamina is involved in the following processes:
 
  • scaffolding  (muscle)
  • separation; mechanical support; cell polarity (epithelial sheet)
  • FILTRATION BARRIER (kidney glomerulus)
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