Lecture 17. Intermediate Filaments and Force Resistance Flashcards
What are some characteristics of intermediate filaments?
Unpolarised
No motors
Less dynamic
Assembled onto pre-existing filaments
Acts like a rope like structure
What structure do all intermediate proteins follow?
~310-355 amino acid coil region which enables two proteins that are either homodimer or heterodimer to twist together and cause a dimeric structure
Head domains between classes are different (can be short or large) and enable interaction with other proteins
Five classes (I-V)
What is the structure of the intermediate filament (IF)?
The defining feature of intermediate filament (IF) proteins is a 310-355 residue coiled-coil domain in each IF molecule flanked by N- and C-terminal blobs (characteristic of each class)
The base unit of the IF is a dimer where the 2 N-termini and C- termini are in close proximity and the coiled-coil region is wrapped around the other. These dimers associate laterally with each other in an anti-parallel fashion and make end-on-end contacts with other dimers where the N- and C-termini of adjacent dimers interact. This results in the formation of a protofilaments. Tetramers of protofilaments are twisted around each other to form the mature IF
How many protofilaments are required to form a protofibril?
4 that twist around each other
What are the function of class I and II IFs?
Class I IF: Acidic keratins
Class II IF: Basic keratins
Both distributed in epithelial cells and both involved in tissue strength and integrity
How do class I and II IF filaments function?
IFs comprised of heteropolymers of class I and II keratins attach to the plasma membrane through desmosomes and the extracellular matrix (basal lamina) through hemi-desmosomes. This provides mechanical strength and integrity to epithelial cells (e.g. in the gut) and their derivatives (e.g. in skin) to resist sheer and pressure forces
What does histology reveal about differential expression of keratins in layers of the skin?
Histology reveals that skin is composed of distinct layers. Keratinocytes in the basal layer express Keratin 5/Keratin 14 (K5/K14) heterodimers. As they move up through the skin to the spinous layer (takes approx. a month in total) they then express K1/K10 heterodimers. Cells in the stratum corneum are dead but nevertheless provide protection to the granular and layers below
What do mutations in the K5/K144 keratins heterodimer produce?
Human blistering disease
Dominant mutant keratin 14 gene lacking either the N and C-terminal domains cannot form protofilaments
Blistering results reminiscent to the human skin blistering disease epidermolysis bullosa simplex (fairly rare)
How do IFs comprised oh heteropolymers of class I and II keratins attach to the plasma membrane?
Through Desmosomes (which mediate cell-cell attachment) and through Hemi-desmosomes (which mediate attachment of cells to the ECM)
This provides mechanical strength and integrity to epithelial cells (e.g. in the gut) and their derivatives (e.g. in skin) to resist sheer and pressure forces.
How are the plasma membrane cells tied together?
By three bonds, two of which are quite weak (tight junction and adherens junction)
Extremely strong attachment known as the desmosome
What are desmosomes?
A cell structure specialised junctional complex, that are localised randomly arranged on the lateral sides of plasma membranes. Desmosomes are one of the stronger cell-to-cell adhesion types and are found in tissue that experience intense mechanical stress, such as cardiac muscle tissue, bladder tissue, gastrointestinal mucosa and epithelia. Desmosomes are composed of a network of the transmembrane cadherins
What are hemi-desmosomes?
Found on the basal membrane of epithelial cells
Contain transmembrane Integrins which interact with proteins in the basal lamina (extracellular matrix) and proteins that interact with type I and II intermediate filaments (cytokeratins)
This ensures adhesion of epithelial cells to the underlying basement membrane and ensures cells can resist shear or stretching forces that would cause loss of epithelial integrity
What are class III IFs?
Desmin, Skelemin, Synemin, Vimentin
Distributed in the muscle, glial cells and mesenchymal cells
Involved in sarcomere organisation and integrity
What is the role of Desmin in both the smooth muscle and skeletal muscle?
In smooth muscle, Desmin binds links Dense bodies together to provide a resistive force to stretching. In skeletal muscle Desmin also prevents overstretch of the sarcomere in skeletal muscle and works in conjunction with two other intermediate filament components (synemin and skelemin) to maintain sarcomere organisation and integrity
What are class IV IFs?
Neurofilaments
Distributed in the neurons
Involved with axon organisation
