Cell Cell interaction Flashcards
Type of cell junctions
Occluding (tight), Anchoring (adhesion and desmo), Comm jx (gap jx)
Function of junctions
Provide str and stability, reg mvmt of solutes ions H20 btwn neighboring cytosolic compartments and across epi layers, convey info btwn cells, Leukocyte rolling
Specific functions of junctions
- Tight - selective permeability
- Adherens - mechanically attach cells and their cytoskeleton (actin fila). Form continuous adhesion bely/ Zonula Adherens
- Desmosomes - attach cells and their cytoskl (IFS) therefore increasing tensile str
- Gap jx - Cell comm, allows free psg of ions AAs sugars nucleotides vitamins 2ndmsgrs(cAMP and IP3), blocks passage of macromolecules (protein, nucleic acid, polysacc) - permeability varies
Tight junctions/Zonula adherens function
Sec and absorb epi (gut), most apical cell jx, tightness modulated by paracrine signals
- Form barrier for most solutes, completly encircle apical end of each cell
- Transmembrane adhesion proteins: Claudin and occludin which bind to intracell ZO proteins (actin-actin cyto)
- Determine epi cell polarity by separating apical domain from basolateral domain; prevents free diffusion of memb protein - maintains directional transport
- Modulates free diffusion of substrates across epi lyrs btwn cells (parallel pathway); AAs and monosac’s from gut lumen.
Caherins
C-C jx use cadherins (Ca dep) to bind subunits
Anchjx=Adherens and Desmosomes
Abundant in epidermis, heart, M (severe mechanical stress locations)
Cadherin composed of?
Intracell anchor proteins - form plaque and connect to actin and IF
Transmembrane adhesion proteins
Adherens Junction
Form continuous adhesion belt (Zonula Adherens) in epi just below tight junctions
Cadherins bind to actin cytoskeleton via catnins
Can contract: morphogenesis, folding epi sheets into tubules
Desmosomes
Button intercell connections, anchor IFs, strong extensive junctions, resists shearing forces in epi cell lyrs, cell-cell interactions mediated by cadherins regulate (motility, proliferation and differentiation, contract inhib)
Desmosome proteins
Cadherin binding cell-cell adhesion dependent on Ca (cad specfici: desmoglein and desmocollin). Intracell anchor proteins = desmoplakan and plankoglobin link to IFs
Desmosome path
- IFs link to cytoplasm plaques
- Plaques connect via cadherins
- Plaques containt intracell anchor proteins desmo(plakin and globin)
Difference between Desmo and Adherins
Ad jxs connect to F-actin not IFs, connect at apical surface (actin rich area) and form continuous belt around cell not spots, linker protein= catenins (important signalling molecule; GI and hepatic cancer)
Gap jxs/Nexus
Free psg of ion and small intracell molecules (Ca, IP3, cAMP, sugars, AA’s, nucleotides) btwn cells (<1.2nm dia). Blocks Macro
Connects cytoplasm via two connexons in intracell space
6 connexin/subunit connexon, few k xin/gapjx
Form continuous aqueous channel btwn cells
Permeability variant
Mediate electrical and chemical coupling btwn cells
Gap jx function: electrical coupling
Some nerve cells - rapid spread of action pot, synch contractions, coordinated depolarization of cardiac muscle, coord contract of sm M, instestine, uterus (birth)
Gap jx function: Chemical coupling
2nd msgrs flow c-c. Hormone (secretin) binds to receptor in pancreatic cancer cells, initiates 2nd msgr cAMP pathway - stims metabolite response (triggers secretion of contents of all sec cells in network (CCK, bicarb, etc)
cAMP -gap jx - other cells therefore stim 1=many activated
Gap jx function: coupled and uncoupled
Important during embryogenesis, reg by Ca. Increased Ca (low pH) closes jx: increased ec Ca, influx into dmg’d cell, close gap jx, insoluble cell, prevents spread of dmg, walls off cardiac infection
Leukocyte adhesion proteins
Selectins = lectins (carb binding prot) L-Selectin = WBC, P-Selectin = Platlets, E-Selectin = activated endo cell
Leukocyte adhesion action
- Lymphocyte homing - L selectin binds oligo (glycoprotein=addressins) on endo of lymphatic organs
- Transient C-C adhesion in bloodstream (leuk rolling) allows WBCs to bind and migrate out of vessel into tissue. Activated endothelial cells express E-Selectin: binds oligo or WBC= weak adhesion - rolling
- Integrin binds ICAM (Ca indep CAMs) on endo cells= strong adhesion = migrate to tissue (diapedesis)
Inflammatory Bowel disease
Crohn’s and ulcerative colitis. Abnorm inflamm response - dysplasia - GI cancer risk.
Trans epithelial migration of neutrophils (PMN) and altered epi barrier function
Downreg of epi TJ protein occluden may play role in enhanced permeability and PMN transmigration observed in active IBD
Autoimmune atk on desmosomes
Pemphigus - blistering and sores. Tx= steroids
Connexin mutations
Connexin 26: Deaf (Cochlear)
Connexin 50: Congenital cataracts - blind (lens)
Connexin 32: X-linked Charicot-Marie Tooth (periph nerves)
Describe Connexin 32 mutation effect
Prog degeneration of periph nerves, M weak, atrophy, impact on deep tendon reflex.
Type 1= Myelinopathy
Type 2=Axonopathy
Mutated leukocyte beta 2
Beta2 Integrin mutation - leukocyte adhesion defect (LAD): impaired leukocyte chemotaxis, extravasation, phagocytosis. Pts suffer from repeat life threatening bacterial infections
Mutated Leukocyte beta 3
Beta 3 Integrin Mut (Platlet) - Glenzmain thrombasthenia. Absence of platlet integrin complex (glycoprotein 2b-3a). No bind to fibrinogen, fail platlet aggregation - def clotting, excess bruising and bleeding
