The cytoskeletal system

Transcription

1 The cytoskeletal system Types, polymerization, characteristics and mechanical properties of cytoskeletal filaments. Associated protein Cytoskeleton The cellular "scaffold" or "skeleton" within the cytoplasm of the eukaryotes and prokaryotes as well. It is composed of proteins. Functions: maintains cell shape (stability) protect the cell enables cellular motion polymerisation using structures such as flagella, cilia and lamellipodia intracellular transport (the movement of vesicles and organelles) endocytosis and exocytosis cell division 1

2 Microtubules Cytoskeleton Intermediate filaments Microfilaments Arrangement of the cytoskeletal components monomers filament bundles (parallel array of filaments e.g. microvillus) network (loosley packed, crisscross filaments) 2D planar (close to plasma and nuclear membranes) 3D (within the cell) Crosslinking proteins!!! (connect and stabilize) 2

3 Actin filaments (Microfilaments) ~ 710 nm wide filaments built up from actin monomers. Functions: force production (contractile and protrusive forces) cell movement (20µm/sec.) muscle contraction (myosin) wound healing defence against infections maintaining cellular shape participation in celltocell or celltomatrix junctions (signal transduction) important role in cytokinesis Microfilaments actin Factin (polymer filamentous) ATP adenosine triphosphate 37nm Gactin (monomer globular) Gaktin (42.3kDa) ~ 375 aminoacid 6.7 x 4 x 3.7 nm 710nm Double stranded, right handed helix 3

4 Actin nucleotide hydrolysis T T D D D D D D D T T D D D D D D D D growing end shrinking end Actin polymerisation The ratio of the actin monomers in the actin filaments (%) nucleation ( lag phase) Critical concentration (nonpolymerising fraction of actin) Formation of oligomers elongation (increasing the size) (low speed RATE LIMITING STEP) steadystate (dynamic equlibrium) rate of association > rate of dissociation time 4

5 Treadmilling The growing at one end of actin filaments is balanced by the shrinking at the other no net growth shrinking end growing end Movement of the filament Intermediate filaments 8 to 12 nanometer wide ropelike filaments. More stable than actin filaments (easy to bend hard to break). Functions: maintenance of cellshape by bearing tension. stabilizing the internal threedimensional structure of the cell (keratin). supporting and anchoring the position of the organelles in the cytosol (vimentin) structural components of the nuclear lamina (lamins) and sarcomeres (desmin) involvement in some cellcell and cellmatrix junctions. Types: vimentins (the common structural support of many cells) keratin, found in skin cells, hair and nails neurofilaments of neural cells (NFL, NFM) Lamin (structural support for the nuclear envelope) 5

6 Intermediate filaments Polymerisation: Monomer Dimer Tetramer two tetramers.filamentum No polarity (no or end)! Microtubules Hollow cylinders (tubes) of about 25 nm in diameter (lumen ~ 15nm in diameter) contain 13 protofilaments (polymers of alpha and beta tubulin monomers). very dynamic behaviour binding GTP for polymerization commonly organized by the centrosome (MTOC: Microtubule Organizing Center). Functions: intracellular transport (associated with dyneins and kinesins). the mitotic spindle (cell division). connection with IC organelles (ER, mitochondrion) 6

7 Microtubules tubulin βtubulin GTP v. GDP dimer 25nm GTP cap GDP GTP protofilament αtubulin polymerisation GTP: Guanosinetriphosphate Actinbinding proteins Functions: Sequestering monomers (profilin thymosin) actin cc in nonmuscle cells ~ 50200µM: ~ 50% monomer facilitate polymerisation (Arp2/3; formin) inhibit polymerisation ( capping protein ) cutting (fragmentation, digestion ) the polymers (gelsolin) crosslinkig (spectrin, fimbrin, αactinin) 7

8 Thymosin profilin Actinthymosin complex works against the filament formation free monomers Actinprofilin complex facilitate the filament formation ARP2/3 70 o Stick to the side of a filament Start the polymerisation (growing) of new filaments 8

9 Microtubule binding proteins Sequestering ( stathmin ) Stabilizing ( MAP:Microtubule Associated Proteins ) Intermedier filament binding proteins crosslinking (plectin) microtubules plectin Intermedier filaments 9

10 The end! 10