Term
| What are the 3 major types of protein filaments that form the cytoskeleton? |
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Definition
- actin filament (5-9 nm)
- intermediate filament (10 nm)
- microtubule (25nm)
accessory proteins (AP): essential for controlled assembly of cytoskeleton motor proteins (type of AP): essential for movement of organelles or filaments
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Term
| function of cytoskeleton? |
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Definition
- 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** |
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Term
| where are each of the filaments located within the cell? |
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Definition
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. |
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Term
| what are the classes of microtubules? |
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Definition
- LABILE: temporary, according to need;dispersed throughout cytoplasm
- STABLE: form permanent parts of cell, including centrioles, cilia, flagella
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Term
| what are important structural features of the microtubule? |
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Definition
- 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
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Term
| Microtubule associated proteins (MAPs) |
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Definition
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
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Term
| components of stable microtubules |
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Definition
- microtubule organizing centers (MTOCs)
- centrosome- cell center MTOC
- basal bodies of cilia, flagella
- axoneme
- motile core of cilia, flagella
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Term
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Definition
- 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)
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Term
| how do the locations of a, b, and γ tubulin differ in microtubulin? |
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Definition
- a, B tubulin are everywhere throughout MT
- γ tubulin ONLY IN MTOC (centrosome)
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Term
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Definition
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 |
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Term
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Definition
- ATP-dependent motor protein involved in transport along a MT from (+) --> (-) end.
- vesicle trafficking and localization of the golgi (inward)
- INWARD MOVEMENT, towards (-) END
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Term
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Definition
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**
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Term
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Definition
- microtubule binding motor protein that uses hydrolysis of ATP to move along it
- moves TOWARDS (+) END
- kinesin = outward movement
- ER movement faciliated by kinesin
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Term
| functions of microtubules? |
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Definition
- organize cell via CENTROSOME
- mitotic spindle formation
- highways for organelle transport (ER, golgi, etc)
- cell MOTILITY (cilia, flagella)
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Term
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Definition
- 2 stranded helical polymers made of G-actin; polymerized into F-actin
- polarity
- ATP binding
- located primarily under plasma membrane
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Term
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Definition
- actin elongation mediated by formins
- formin dimer forms on (+) end and directs motion in that direction
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Term
| actin cross-linking proteins |
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Definition
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
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Term
| what actin cross linking proteins are associated with micovilli's structure? |
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Definition
these 2 proteins' crosslinking accounts for microvilli's shape |
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Term
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Definition
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
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Term
| functions of actin filaments |
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Definition
- muscle contraction (myosin II binding)
- anchoring junctions (cell-cell; cell-matrix)
- cleavage furrow in dividing cells
- development of tubes (epithelial)
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Term
| key features of intermediate filaments |
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Definition
- NOT ATP or GTP DEPENDENT (but maintains dynamism via phosphorylation)
- assembly along ENTIRE length, not just as ends
- easily bent, but difficult to break
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Term
| location and other key features of intermediate filaments |
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Definition
- integrate with MT and actin
- anchoring junctions via:
- DESMOSOMES (cell-cell)
- HEMIDESMOSOMES (cell-matrix)
- span cytoplasm from one junction to another, lending TISSUE STRENGTH
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Term
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Definition
- keratins (epithelia)
- vimentin (mesenchymal cells)
- desmin (muscle cells)
- glial fibrillary acidic protein (GFAP)- astrocytes
- neurofilaments (neurons)
- lamins (nuclear lamina)
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Term
| what are classic functions of intermediate filaments? |
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Definition
- structural support against rupturing forces
- nuclear lamina formation (via lamins)
- immunologic markers for ID of cells and corresponding tumors
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Term
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Definition
- a microtubule specific drug
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- prevents polymerization
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- gout treatment
colchicine |
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Term
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Definition
microtubule specific drug prevents polymerization (prevents mitosis) anti-cancer drug
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Term
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Definition
intermediate filament specific toxin causes disassembly or rearrangement of IF neurotoxin
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Term
| epidermolysis bullosa simplex |
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Definition
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
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Term
| the cytoskeleton can experience negative changes secondarily through injury. what are some of the ways? |
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Definition
- 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
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Term
| what are the classes of cell junctions? |
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Definition
- occluding: tight junctions
- anchoring
- actin filament association- cell/cell (adherens junctions); cell/matrix (focal adhesions)
- intermediate filament association- cell/cell (desmosomes); cell/matrix (hemidesmosomes)
- communicating (channel forming): gap junctions
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Term
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Definition
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.
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Term
| zonula adherens/ adhesion belt |
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Definition
adherens junction cell-cell: actin filaments from one cell to another linked by CADHERIN DIMERS
actin filament,
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Term
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Definition
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) |
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Term
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Definition
- 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
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Term
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Definition
intermediate filament cell-cell adhesion junction cells joined by CADHERIN-FAMILY adhesion proteins (desmoglein; desmocollin) |
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Term
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Definition
autoantibodies against desmoglein deposition of immuniglobulin along plasma membranes of epidermal keratinocytes, leads to severe blistering |
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Term
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Definition
transmembrane integrins attach cell to matrix matrix components: collagen, laminin, etc BOLLOUS PEMPHIGOID: antibody against hemidesmosome binds at dermoepidermal junction non-acantholytic blistering |
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Term
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Definition
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
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Term
| why are gap junctions important? |
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Definition
- facilitate metabolic and electrical coupling between cells
- coordinate actvities in epithelia, smooth muscle, heart muscle
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Term
| what effect does calcium have on gap junction permeability? |
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Definition
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*
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Term
| components of extracellular matrix? |
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Definition
- polysaccharides +/- protein
- GAGs
- proteoglycans
- glycoproteins
- fibrous and adhesive proteins
- collagen
- elastin
- fibronectin
- laminin
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Term
| what are the four main GAG groups and what are they most responsible for? |
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Definition
- HYALURON: connective tissue
- CHONDROITIN & DERMATAN SULFATE: cartilage, skin (related to aging)
- HEPARAN SULFATE: basal laminae, cell surfaces
- KERATAN SULFATE: cornea, cartilage
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Term
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Definition
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
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Term
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Definition
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)
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Term
| network forming collagen (IV, VII) |
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Definition
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
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Term
| structural features of collagen |
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Definition
- fiber (LM detection)
- fibril (EM detection)
- molecule: tropocollagen
- striations come from staggered arrangement
- cross-banding pattern
- rich in PROLINE and GLYCINE
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Term
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Definition
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
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Term
| collagen-associated diseases |
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Definition
- 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
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Term
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Definition
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
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Term
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Definition
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
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Term
| diseases related to elastin |
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Definition
- marfan syndrome: fibrillin gene mutation
- elastic tissue defects, including tendency of aorta to rupture
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Term
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Definition
responsible for linking ECM components to each other and to cells |
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Term
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Definition
- 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
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Term
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Definition
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
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Term
| what is the difference between basal lamina and basal membrane? |
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Definition
the terms are NOT synonymous basal membrane = lamina + underlying collagen fibers
also, remember that the lamina has 2 layers: LAMINA RARA & LAMINA DENSA
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Term
| functions of basal laminae |
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Definition
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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