Regulation of Cytoskeletal Filaments
Pages 992-1010
Most cytoskeletal regulation is performed by accessory proteins that bind to either the filaments of their free subunits.
Microtubule-organizing center (MTOC) – a specific intracellular location where microtubule nucleation occurs
Nucleation of Microtubules by gamma-tubulin
- end + end
The Centrosome, a MTOC
50 gamma-TuRC
Cross-section of a Centrosome
Centriole
The centrioles organize the centrosome matrix ensuring its duplication during each cell cycle
Centrioles are composed of a short cylinder of modified microtubules and a large number of accessory proteins
Neither fungi nor most plants have centrioles
Center-Seeking Behavior of a Centrosome
Reorganization of Microtubules
Nucleation by the ARP Complex
ARP – actin-related protein, each ARP is about 45% identical to actin
Structures of Actin, Arp2, and Arp3
Actin Web Formation
Binding of Profilin and Thymosin
About 50% of actin in nonmuscle cells is in filaments and 50% as soluble monomers
Profin bound to Actin Monomer
Profilin binds to the opposite side of the ATP-binding site, blocking the side of the monomer that would associate with the filament minus end, allowing this complex to add onto a free plus end
+
-
Effects of Thymosin and Protilin on Actin Polymerization
Effects of Stathmin on Microtubules
Stathmin’s binding to tubulin is inhibited by the phosphorylation of stathmin
Organization of Microtubule Bundles
MAP – Microtubule-associated protein
MAPs have at least 1 domain that binds to the microtubule and another that projects outward
Localization of MAPS in a Neuron
-MAP2 protein stained orange in the cell body and dendrites
-tau stained green in the axon
Actin Filament Twisting Induced by Cofilin
Cofilin – is a small protein that binds actin in a 1:1 ratio and destabilizes actin filaments
Tropomyosin – an elongated protein that bind simultaneously to 7 actin monomers and stabilizes actin filaments
Filament Capping Changes Filament Dynamics
CapZ – Capping protein
Capping is regulated by intracellular signals, PIP2 (Phosphatidylinositol 4,5-bisphosphate) uncaps + ends
Proteins Binding Microtubule Ends
Proteins that bind to the ends of microtubules can control microtubule positioning
Cross-linking Cyoskeletal Elements
Red – MicrotubulesBlue – Intermediate FilamentsGreen – Cross-linking protein, Plectin
Plectin also links IF to actin filaments and microtubulesFilaggrin bundles keratin filaments in the epidermis of the skin to give it its toughness
Various Actin Arrays
Actin Cross-linking Proteins
Formation of 2 Types of Bundles
A Micorvillus
Filamin Cross-links Actin into a 3-Dimensional Network
Loss of Filamin Causes Abnormal Cell
Motility
Actin formed by filamin is required for cells to extend the thin sheet-like membrane projections call lamellipodia
Filament Severing Changes Filament Dynamics
Microtubule Severing
Red - Microtubules
Actin Filament Severing by Gelsolin
-Activated by high levels of cytoplasmic calcium
-No energy needed
-Gelsolin is removed by PIP2
Severing of microtubules by Katanin-made up of 2 subunits, one for severing and the other for targeting it-the process requires ATP
Platelet Activation
Platelet Activation
Focal Contacts in Fibroblasts
Focal contacts –highly specialized type of attachment between actin filaments and the extracellular matrix
Effects of Extracellular Signals