The Cytoskeleton Lecture Notes PDF

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Cellular and Molecular Biology The Cytoskeleton:  Network of protein filaments extending throughout cytoplasm of all eukaryotic cells  Function o Structure and support o Basis for cell migration and cell movement  Intracellular transport  Contractility and motility o Basis for growth and regeneration  3 cytoskeletal fibres o Intermediate filaments  Types  Acidic/ basic o Keratins  Keratin filaments anchored to plasma membrane in specialised regions of cell contact  Desmosomes o Cytoplasmic side  Associated with dense plaque  Mediated by extracellular cadherin proteins  Anchored to both sides of desmosome serve as mechanical link between adjacent cells  Provides mechanical stability to entire tissue o Epithelial cells  Lamins o A o B o C o Nucleus  Desmin o Muscle  Peripherin o Peripheral neurones  GFAP o Glial cells  Neurofilaments o NF-L o NF-M o NF-H

Cellular and Molecular Biology Common structure  Central alpha-helical rod flanked by amino and carboxy terminal domains  Central helical rods form coiled-coil dimers o Dimers associated in staggered antiparallel tetramers that assemble as protofilaments  Protofilaments wrap in ropelike fashion  Non-polar  10 nm diameter  Associated with cell membrane and nuclear envelope  Basic structural role o Microtubules  Polymers of single globular protein – tubulin  Tubulin – dimer consisting of two polypeptides o Alpha and beta tubulin o Member of small monomeric G-proteins o Tubulin subunit  Binds GTP  Alpha tubulin binds GTP but does not hydrolyse it o Low GTPase activity  Beta tubulin binds GTP and rapidly hydrolyses it to GDP after polymerisation  GDP/ GTP tubulin dimers depolymerises more easily than GTP/ GTP tubulin dimers  GTP-dimer cap retained at growing end  If GTP/ GTP-tubulin falls  Hydrolysis rate is faster than cap rate o GDP/ GTP-tubulin depolymerises from both ends  Radiate from centrosome  Primary microtubule organising center o Orients most microtubules and determines cell polarity  Rigid hollow tubes 

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Features

Cellular and Molecular Biology Undergo continual assembly and disassembly Involved in cell movement o Intracellular transport of organelles  Microtubule associated proteins  Microtubules and microtubule motor proteins  2 families o Kinesins  Dimer  Head domain  Binds to microtubules tail domain binds to cargo vesicles  Moves towards positive end of microtubule o Dyneins  Move towards negative end of microtubule  Associated with microtubule motors  Structure  Subunits aligned end to end in protofilaments  13 linear protofilaments form around a hollow core  Microtubules are polarised  Rapid growing positive end  Slow growing negative end  24 nm diameter o Microfilaments  Polymer of actin monomers  Organised into higher order structures o Bundles o 3-D networks  Major features  Polymerisation and depolymerisation o Polymerisation  Reversible  Occurs preferentially at one end  Treadmilling o Under regulatory control  Crosslinking into bundles and networks  Association with membrane  

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8-9 nm diameter Assembly and disassembly of actin filaments

Cellular and Molecular Biology  

Individual actin monomers globular (G actin – 375 amino acids) Polymerises to form filaments (F-actin) o Actin monomer – consist of polarised amino acids orientated in same way within filaments o F-actin = polarised o Reaction requires binding of ATP (From G-actin to F-actin)  ATP-F-actin slowly hydrolysed to ADP-Factin  ADP-F-actin depolymerises much more readily than ATP-F-actin...