Hitchcock - Cyto1 Flashcards
Actin filaments
Made up of actins. Actins have two different ends so the molecule is polar. Have a bound ADP or ATP. Has + end and - end (actin filament is polar). Has many proteins that can bind to it and alter its dynamics. Can be capped, severed, cross-linked etc. Has ATP or ADP bound to it. The rate limiting step is nucleation. Once the nucleation (3 subunits” occurs there is rapid growth. Whether you have ADP or ATP will alter the stability of the end. The extreme + end will have ATP, the others will have ADP.
Tubulin and mirotubules
Tubulin is made up of alpha and beta subunits. The beta subunit is the one that binds GTP. Microtubule is made up of tubulin. Has + and - end. Each microtubule has 13 protofilaments, which means that in one circle of microtubule there are 13 columns of tubulin. Cilia, flagella, centrioles. Most cells also have a primary cilia, which is non-motile and play a role in signaling and developent. The main difference between the non-motile cilia and regular cilia is that the non-motile ones do not have the “outer knobs” called dynein, which is the motor for cilia and flagella (other difference is the lack of the central pair in the middle).
Centrosome
Organized around a pair of centrioles. Contains a gamma tubulin ring complex, which nucleates and caps the - end. This causes the + ends to be oriented towards the outside of the cell.
Dynamic Instabiity of mirotubules
the + end transitions between growth and shrinkage. If the GTP cap (or ATP in actin) is lost you will see a catastrophic event and the microtubule will shrink. All depends on whether or not the microtubule components are either in the GTP or GDP (or ATP/ADP in actin) state.
Microtubule Associated Proteins (MAP)
There are proteins that regulate the stability of microtubules by binding either one of the ends or on the side. Tau is one example.
Tau
component of neurofibrillary tangles in Alzheimer’s. Side-binding protein of microtubules - microtubule associated proteins (MAP)
Intermediate filaments
Involved with keratin, so hair, fingernails, etc. Made up of a coiled-coil structure of two antiparallel fibers. Two of these structures then come together to form a tetramer. 8 tetramers then come together to form 1 intermediate filament.
Establish cell polarity, the borders of the cell, and are stress absorbers. No motors. Extend from outside of the nucleus to the border of the cell. Not involved in directional transport because the cells are not-polar.
Phalloidin
Colchicine
Taxol
P - Binds and stabilizes actin filaments. Found in death angel mushroom. Also contain alpha amanitin. WIll cause liver failure
C - depolymerizes microtubules
T - stabilizes microtubules, anti-cancer drugs.
Actins role in movement
Generally motility has to do with actin polymerization. At the leading end is actin driven. At the following end is myosin driven. Example is neutrophil.
1) elongation of the barbed end
2) sever actin filaments so that you can have more + ends
3) form branches from existing actin filaments (using the arp2/3 complex)
Arp2/3
Nucleates filaments from the sides of actin filaments like branches of a tree, which come off of the actin filament and you have more + ends to make the polymerization happen. Can be activated by integrins via a downstream pathway of phosphorylation etc. Causes nucleation of branched filaments. They push against the cell membrane. Involved in neutrophil migration, wound healing, metastasis, bacterial infections, endocytosis, etc. Can be hijacked by lysteria.
lysteria
Has a homolog of one of the things that activates the Arp2/3 protein on it’s surface. Therefore, it can get inside via phagocytosis (there is plenty of actin in the cell) and nucleates actin polymerization off of the tail of the bacteria. It makes protrusions in the cell so that it can hop from cell to cell. it is able to zoom through the cell pretty easily, driven by th force of actin polymerization. Lysteria goes into intestinal epithelium.
+ tip proteins
will bind to and track the growing end of the microtubule. These are important for communication with the cell and connection with the periphery of the cell (cell cortex).
