Connecting the cytoskeleton to the cell exterior Flashcards
What does the extracellular matrix do?
Provides structural support tocellsand tissues but also controls cell migration, proliferation and differentiation
What do cell-cell junctions do?
Links to the cytoskeleton via
tight junction
adherens junction
desmosome
Components of tight junctions
TJs are composed of the tetraspan membrane proteins, Claudin and Occludin, and TJ-associated proteinsincluding a family ofZona Occludens proteins(ZO-1, ZO-2, and ZO-3) which associate not only to the intracellular domains of Claudin and Occludin but also bind directly to F-actin and other actin-regulatory proteins including cortactin, α-actinin and Type 1 Myosin.
Components of adherence junctions
They are continuously assembled and disassembled, allowing cells within a tissue to respond to forces, biochemical signals.
AJs are composed of E-Cadherins, a family of transmembrane proteins that form homodimers with other E-Cadherin molecules on adjacent cells and other proteins including b-catenin and a-catenin which links the inner face of E-Cadherin to actin filaments.
Components of desmosomes
Desmosomes are composed of a network of the transmembrane cadherins, Desmoglein and Desmocolin,and adaptor proteins, Plakoglobin and Plakophilin, which help secure Desmoplakin to Keratin (Type I and II intermediate filaments) to the desmosome structure.
Use and components of keratins
Intermediate filaments comprised of type 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 the extracellular matrix do?
Compartmentalizes tissues
Serves as a highway for cell migration
Presents signaling molecules (e.g. TGFb)
Provides structural support
What is the EM made of?
- Fibrous proteins such as collagen and elastin, which make fibers that provide strength and flexibility
- Hydrated gel-like matrix containing protein-polysaccharide complexes called proteoglycans, which are glycoproteins with glycosaminoglycan (GAG) linkages.
- Adhesive glycoproteins such as fibronectin and laminin, that link components of the matrix to one another and to cells via cell surface receptors e.g. integrins.
Integrins role in EM
Integrins connect proteins in the basal lamina (EM) with hemi desmosomes which provide an attachment site for type I and II IF’s
Importance of integrins
Integrins are crucially important because they are the main receptorproteins that cells use to both bind to and respond to the ECM.
Integrins also activate intracellular signalling pathways that communicate to the cell the character of the ECMthat is bound.
Many integrins recognize the RGD sequences in the adhesive glycoproteins such as Laminin and Fibronectin.
Integrin tails interact with cytosolic proteins that link integrins to intracellular cytoskeleton.
Components of the adhesive glycoprotein: laminin
Laminin consists of three long polypeptides α, β, and γ.
Disulfide bonds hold the polypeptides together in the shape of a cross. Laminins have several domains, including binding sites for components of the ECM proteins including type IV collagen and other accessory proteins and a distinct domain which enables binding to integrin receptors on cell surfaces.
Since integrins are transmembrane receptors this association tethers the basal lamina to the cell membrane.
Components of adhesive glycoproteins: Fibronectin
Fibronectins are a family of closely related glycoproteins in the ECM that help guide cell movement. Fibronectin has two large subunits linked near the C-terminals by two disulfide bonds.
Each of the two Fibronectin subunits is folded into a series of rod-like domains which bind one or more ECM macromolecules, including several types of Collagen. Other domains of Fibronectin recognize cell surface receptors (Integrins) via a RGD (arg-gly-asp) sequence. This enables Fibronectin to act as a bridging molecule between cells and the ECM.
