Term 2 Lecture 9: Junctions And ECM Flashcards
Gap junctions
Form passageways between adjacent cells
Allow chemical communication
Present in most mammalian tissues
Composed of connexin proteins
Gap junction channel is composed of 2 connexin hemichannels : connexin hexamers
Size limit for molecules that can pass through gap junctions up to 1000MW in size ( but a long thin molecule of higher molecular weight may also be able to pass through) allowing through:
Ions, low MW precursors of cellular molecules, products of intermediary metabolism, small signalling molecules.
Superficial semblance to nuclear pores (100nm) but gap junctions are far smaller (9nm) with a transport channel of only 1.4nm.
Enable passage of ions into neuronal tissue and cardiac muscle cells for electrical signalling
Allow second messengers such as Ca²+ transfer to other cells
Allow transfer of nutrients to cells that cannot produce them (e.g. oocytes from surrounding cells - egg cell in ovary receives nutrients via gap junction from nurse cells)
Gap junctions in disease
Mutations in connexins cause at least 8 human diseases including a form of deafness, a form of progressive degeneration of peripheral nerves and a condition with heart malformations (affects tissue development)
Plasmodesmata (only in plants)
Plant cell wall is a barrier for cell to cell communication
Direct communication is possible through plasmodesmata that extend from one cell to another through the wall.
Desmotubules: plasma membranes merge to form a continuous channel.
Plasmodesmata may contain an extension of ER
Actin network: cytoskeletal filaments may continue through plasmodesmata
Viruses and signalling molecules can pass through them.
Adhesion summary
Cell-cell junctions are important in tissue integrity, cell polarity and cell-cell communication
Anchoring junctions: adherens and desmosomes
Tight: seal between cells controlling paracellular transport and lipid movement
Gap: allow communication between cells
Plants also have plasmodesmata for “ “ “
The ECM
- complex arrangement of molecules
- inbetween cells
- Highly organised
- mostly connective tissues: tendons, cartilage, bone or dermis of skin
- diverse structures created by different proportions and arrangements of ECM components
- cells secrete ECM and it is assembled outside the cell
- cells have ECM receptors - the integrin family
Connective tissue and the ECM
Provides physical strength and structural support to withstand mechanical forces e.g. pressure on skin
- fibroblasts are the primary cells that secrete ECM
- influences cell shape and behaviour
- for storage and presentation of some growth factors and other bioactive molecules - held inactive in ECM and mobilised in response to certain signals
- involved in tissue repair mechanisms e.g. if you cut your skin fibroblasts produce more ECM for other cells to populate and create tissue for repair
Major types of ECM molecule
Glycosaminoglycans: polysaccharide chains usually found attached to proteins forming proteoglycans
Fibrillar proteins:
Collagen - mainly structural role, provide mechanical strength
Fibronectin: adhesive glycoprotein
Elastic fibres: (in some tissues) allow stretch e.g. in stomach and skin
+ Networks of other fibrillar proteins
Hemidesmosomes and focal adhesions
Attach plasma membrane to ECM, linked to IFs and actin.
EBS: keratin IFs
+ inner and outer plaques (HD) on plasma membrane
JEB: lamina lucida* located in subbasal dense plate
DEB: lamina densa* and anchoring filaments that link to ECM
- Lamina lucida + lamina densa make BL
Integrin alpha 6 beta 4 heterodimer transmembrane proteins
Integrins link to laminin in the ECM
Integrins link cytoplasmic keratins (IFs) via plakins (plectin and BP230)
Laminin
Inserts the adaptor protein that attaches hemidesmosomes to the ECM.
Laminin knockout decouples desmosomes from the basal lamina causing deformities and skin blistering due to tissue malformations leading to epidermis becoming detached from the dermis
Hemidesmosome summary
They anchor epithelial cells to the ECM
Link IF network to ECM
Transmembrane integrins linked to IFs via adaptors (plakins)
Integrins link to ECM via laminin
Basal lamina
Part of ECM but a distinct strong filamentous layer
Plasma membrane - thin, sheet-like network that anchors epithelial cells
Laminin layer (perlecan and laminin) -
Attached to cells via hemidesmosomes
Nidogen/ enactin -
Physical support, developmental control, filtering functions
Collagen lV layer -
Major constituents: laminins, collagen lV, nidogens, heparan sulphate, proteoglycans (perlecans)
Aka basement membrane as it resembles a membrane under a microscope however it is infact not a membrane
Laminin
Forms a network with collagen lV and other proteins to form the basal lamina
Laminin+lV collagen+enactin+perlecan
Form the basal lamina, the cell is anchored to this network via integrins (plasma membrane integral proteins)
Laminins are cruciform complexes consisting of 3 polypeptide chains that form tight networks in the ECM. They bind to other ECM proteins e.g. collagen and to cell surface receptors e.g. integrins
See notebook 2 for diagrams.
They self assemble into network structures that line the bottom layer of epithelial cells.
Have an alpha, beta and gamma chain with alpha helical coiled coil and LG domain that bonds cellular receptors
Basal lamina
3 distinct patterns
Epithelial
Muscle myotubules - ECM connects muscle cells closely packed (like honeycomb) creating strength and flexibility under major force
Kidney glomerulus - basement membrane links endothelial cells in blood vessels to the podocytes acting as part of the filtration system of the kidney
Interna+densa+externa
= Glomerular basal lamina
(See diagrams end of notebook 2)
The collagen family
- most abundant ECM protein
- triple helical domain (mostly)
-27 types
Collagen biosynthesis
ER: occurs in ER, cleaved single peptide, hydroxylation of pro and lys, glycosylation, disulphide bond formation (trimer formation)
Golgi: trafficked through golgi (cisternal progression), lateral association of procollagen, trafficked to plasma membrane and secreted (exocytosis)
Extra-cellular: cleavage of propeptides from N and C termini by procollagen N-proteinase and procollagen C - proteinase. Fibril self assembly, crosslinks formed via hydroxylysines (catalysed by lysyl oxidase.) Finally assembly with other collagens and proteoglycans.
