• the stabilizing components of the cytosol
• maintains external shape and internal structures
• regulates internal and external movements

• Microtubules (25 nm)
• Intermediate filaments (10 nm)
• Actin filaments (5-9 nm)

• 2-stranded helical polymers
• flexible aggregates of filaments organized in linear bundles, two dimensional networks, and three-dimensional gels
• mostly beneath the plasma membrane
• CELL SURFACE ORGANIZATION
• actin anchoring junctions

• hollow cylinders
• long, rigid, and straight hollow cylinders
• one end attached to MTOC (centrosome or basal body)
• CELL HIGHWAYS

• ropelike fibers
• heterogeneous family of ropelike fibers spanning the cytoplasm from one cell-cell junction to another
• also form the nuclear lamina
• TISSUE STABILITY
• Intermediate Filaments anchoring junctions

• not fixed streets, rather "ant trails"
• actin and microtubule cytoskeleton reorganizes rapidly during mitosis

• microtubules are polymers of tubulin alpha and beta.
• the wall of each microtubule consists of 13 protofilaments
• microtubules have an inherent polarity, i.e. they have a dynamic (+) end and a more inert (-) end
• the (-) end needs to be stabilized in a MTOC
• growing and shrinking occurs at the (+) end
• GTP binding to tubulin causes the microtubule to grow in a linear configuration
• GTP hydrolysis causes the microtubule to depolymerize and shrink

• involved in tubulin polymerization leading to stabilization of microtubules
• thus, the formation of functionally differentiated cytoplasm is promoted, e.g. the axons of neurons

• leads to the opposite reaction performed by MAPs
• leads to microtubule destabilization (or catastrophe)

• Centrosome: Cell center MTOC
• Basal bodies of cilia & flagella

• Motile core of cilia & flagella
• built from microtubules and dyneins
• all have a core of longitudinally arranged microtubules
• 1. Clilia (9 peripheral doublets+ 2 central singlets pattern)
• 2. Flagella (9 peripheral doublets + 2 central singlets pattern)
• Basal body (a MTOC giving rise to a cilium or flagellum; it has a 9 peripheral triplets + 0 central pattern).

• a pair of centrioles: 2 short cylinders at right angles to each other, composed of modified microtubules
• the pericentriolar cloud or material, or centrosome matrix, containing gamma tubulin ring complexes;pericentriolar material provides the sites for the intitiation of the microtubule polymerization (nucleation)
•  (-) ends of the microtubules are embedded in this

• A specialized centriole (MTOC) that gives rise to the axoneme of a cilium or a flagelum.
•  
• Has a 9 microtubular triplets radially arranged in a pinwheel fashion (9+0 axoneme pattern)

• form bridges between neighboring doublets

• caused by the genetic lack of dynein arms

• proteins that bind to a polarized  cytoskeletal filament and use energy from repeated ATP hydrolysis to move along it
• 2 types: (Actin binding, Microtubule binding)

• Kinesin: movement towards the (+) end of the microtubule
• cytoplasmic Dynein: movement towards the (-) end of the microtubule, i.e. towards the cell center. (closely related to the ciliary dynein)
• locations of the ER and the Golgia are due to the movements induced by kinesin and dynein

• organize the cells (centrosome)
• form mitotic spindle
• provide highways for organelle transport (intracellular movement, e.g. along axons)
• cell motility (external movements: cilia flagella)

• two-stranded helical polymers composed of G-actin. Polymerized into F-actin
• also have polarity
• ATP binding

• mediate actin elongation on the plus end

• keep external cell shape (cortex)
• muscle contraction
• participation in anchoring junctions (Cell-cell & Cell-matrix)
• microvilli formation
• cleavage furrow in dividing cells
• cell polarity
• development of tubes

• rope-like
• tetramers with no polarity
• not dependent on ATP or GTP for polymerization, but still dynamic (phosphorylation)
• assembly along entire length, i.e. along their length as well as ends
• easily bent but difficult to break
• integrate mechanically with MT and Actin MF
• participate in anchoring junctions (cell-cell desmosomes & cell0matrix hemidesmosomes)
• spanning the cytoplasm form one junction toanother --> tissue strength

• Vimentin: Mesenchymal cells
• Desmin: Muscle cells
• Glial fibrillary acidic protein (GFAP): Astrocytes

• Structural support against rupturing forces.
• Nuclear lamins from the nuclear lamina
• Immunologic markers for identification of cells and corresponding tumors

• Actin-specific drug
• Prevents polymerization

• Actin-specific drugs
• Stabilizes filaments (leucocytes cannot move effectively)

• Microtubule specific drug
• Prevents polymerization (gout treatment)

• Microtubule specific drugs
• Prevent polymerizaiton (preventing mitoses:antcancer drugs)

• Intermediate Filament-Specific Toxins
• Acrylamide: disassembly or rearrangement of IF (neurotoxin)

• Blistering of the skin caused by a mutant keratin gene

• Lou Gehrig's disease
• Alzheimer disease
• Alcoholic liver disease
• HPV infection-->Koilocytosis

• Outer leaflets of adjacent plasma membranes fuse to form a zone around the entire apical perimeter of the cells
• restrict the mobility of membrane proteins and passage of molecules between cells

• Claudin
• Occludin

• Link cytoskeleton of adjacent cells
• Link cytoskeleton to extracellular matrix

• Cell-cell: Zonula adherens (Adhesion belt; intermediate junction)
• Cell-matrix: Focal contacts/Adhesion

• Cell-cell: Desmosome (macula adherens)
• Cell-matrix: Hemidesmosome

• Autoantibodies against desmoglein
• Deposition of immunoglobulin along the plasma membranes of epidermal keratinocytes (Immunofluorescence) -->Severe blistering
• separation in desmosomes

• Integrins attach cell to matrix

• Antibody against hemidesmosome binds at the dermoepidermal junction
• Gross and microscopic appearance of subepiderma, non-acantholytic blisters

• Facilitate metabolic and electrical coupling between cells.
• Coordinate activities in epithelia, smooth muscle, heart muscle
• communication between oocyte and surrouonding granulosa cells. mutation-->infertility

• Polysaccharides+/- Protein: GAGs and Proteoglycans
• Fibrous & adhesive proteins: Collagen, Elastin, Fibronectin and Laminin

• Long, unbranched polysaccharide chains composed of repeating disaccharide units
• One of the two sugars is always an amino sugar, usuall sulfated (except in hyaluronic acid)

• Hyaluronan: Most connective tissues
• Chondroitin & Dermatan sulfate: Cartilage and skin (rel. to aging)
• Heparan Sulfate: Basal laminae, cell surfaces
• Keratan sulfate: Cornea and cartilage

• Binding messenger & secretory molecules
• Structural and functional role in basal laminae: Selective sieves
• Can be integral components of plasma membrane, acting e.g. as coreceptors

• Fibril-forming (fibrillar): I, II, III, V, XI
• Fibril-associated (lateral association): IX, XII
• Network-forming: IV (basal laminae), VII (anchoring fibrils)

• Fiber: seen by LM
• Fibri: seen by EM
• Collagen molecule: Tropocollagen
• Cross banding pattern
• Extremely rich in proline and glycine

• Like collagen rich in proline and glycine, but not glycosylated and without hydroxylsine
• Cross linking of basic molecule (tropoelastin) similar to collagen.
• The elastin core is covered by sheath of microfibrils (incl. Fibrillin)

• Fibrillin gene mutation
• elastic tissue defects

• Fibronectin
• Laminin
• Responsible for linking ECM components to each other and to cells

• Scaffolding
• Separation: Mechanical
• Suppor: Cell polarity
• Filtration barrier

• Alport's Syndrome: Missing BL components
• Goodpasture's Syndrome: Antibodies against BL components

• permits ions, and small molecules (less than 1000 daltons) to pass from cell-to-cell, through their central channel

• separate the opposing plasma membranes by a 2-4 nm gap in gap junctions
• each connexon consists of six identical protein subunits (connexins) arranged radially around a central channel

• The cross-banding is the result of the arrangement of tropocollagen molecules comprising the fibril
• the collagen polecule (tropocollagen) is a rod-shaped molecule measuring 300nm in length.
• the typical cross-banded repeat every 67 nm along the collagen fibril is due to the staggered parallel arrnagement of the tropocollagen molecules, and their ability to permit heavy metal stains from penetrating the fibril

a. Preprocollagen synthesis (Pro-alpha chain)

b. Hydroxylation of selected prolines and lysines

c. Glycosylation (of selected hydroxylysines)

d. Procollagen formation (triple helix)

e. Secretion of procollagen

A large adhesive glycoprotein that has domains specialized for binding itself, collagen, fibrin, proteoglycans and cell surfaces (via the integrins).

The fibronectin receptor (an integrin) is a transmembrane glycoprotein that links fibronectin (in ECM) with cytoskeleton (in cell). Fibronectin molecules assemble into fibrils only on the surface of certain cells.

There is also a plasma fibronectin that functions in blood clotting, wound healing and phagocytosis.

• Consists of the basal lamina plus the undelrying reticular lamina