Week 11- Cell interactions and junctions - lecture notes.pdf

BMS1025 – Cell Biology Cell interactions and junctions Social cells Cell junctions: Tight Anchoring Communication Dr Patrizia Camelliti [email protected] Alberts 5th Ed: Fig 19-27 & 35 Social cells Cells do not exist in isolation; the interact physically and chemically with one another...

BMS1025 – Cell Biology Cell interactions and junctions Social cells Cell junctions: Tight Anchoring Communication Dr Patrizia Camelliti [email protected] Alberts 5th Ed: Fig 19-27 & 35 Social cells Cells do not exist in isolation; the interact physically and chemically with one another Transmembranous glycoprotein receptors at the cell surface “read” chemical signals within the body Most cells are physically attached to their surroundings: • Specialized cell junctions occur at points of cell-cell & cell-matrix contact in all tissues: particularly plentiful in epithelia • Visualized using freeze fracture electron microscopy: reveals interacting plasma membranes (& often underlying cytoplasm & the intervening intercellular space) are highly specialized in these regions Alberts 5th Ed: Fig 19-25 Cell junctions Classified into three functional groups: Occluding or tight junctions: seal epithelial cells together tightly to prevent even small molecules from leaking from one side to the other Anchoring junctions: mechanically attach cells to their neighbours or to the extracellular matrix Communicating junctions: mediate the passage of small molecules from one cell to the next Alberts 5th Ed: Fig 19-3 Occluding junctions Also called tight junctions or zonula occludens • Closely associated areas of two cells: a virtual impermeable barrier • Typically found in epithelial sheets • Formed by claudin & occludin proteins • Transmembranous glycoproteins in the membrane epithelial cells • Interact to seal the two membranes together Alberts 5th Ed: Fig 19-26 Tight junctions: Roles Perform three vital functions: Hold cells together Prevent passage of molecules between cells Materials must enter cells to cross the tissue Controls what is passes through e.g. the blood-brain barrier Block movement of membrane proteins between regions of cell, allowing specialized functions e.g. receptor-mediated endocytosis at the apical surface & exocytosis at the basolateral surface of gut epithelium Epithelia classed as 'tight' or 'leaky' depending on the numbers of tight junctions Tight epithelia: blood brain barrier gut epithelium Leaky epithelium: kidney tubules Alberts 5th Ed: Fig 19-24 Tight Junctions Alberts 5th Ed: Fig 19-25 Anchoring Junctions: Functional types Anchoring junctions occur in two functionally different forms: Cell to cell anchors • Adherens junctions & desmosomes hold cells together • formed by transmembrane adhesion proteins that belong to the cadherin family • 24 members: interact with one another to join specific cells together • Intercellular space is very wide (~30nm) Anchors to extracellular matrix • Focal adhesions & hemidesmosomes bind cells to the extracellular matrix especially to basement membranes • formed by transmembrane adhesion proteins of the integrin family Alberts 5th Ed: Fig 19-4 Anchoring Junctions: Links to cytoskeleton On the cytoplasmic side adhesion proteins interact with the cytoskeleton: Adherens junctions (& focal adhesions) • Link to the actin cytoskeleton via a protein complex Transmembrane protein (cadherin or integrin) Protein complex Actin filament Alberts 5th Ed: Fig 19-14 & 15 Function: Adherens Junctions • • Links cells into sheets & tissues Coordinate actin cytoskeletons • In epithelia: adherens junctions can form an adhesion belt (zonula adherens) encircling the cell Suppors transcellular network of actin beneath PM e.g. co-ordinated action of actin filaments during development forms epithelial tubes from sheets • In non epithelial cells: small, punctate attachments link actin cytoskeletons e.g. in heart organises contractile unit: actin linked end-to-end from one cell to the next Alberts 5th Ed: Fig 19-16 Anchoring Junctions: Links to cytoskeleton On the cytoplasmic side adhesion proteins interact with the cytoskeleton: Cell-cell Cell-ECM Desmosomes & hemidesmosomes (macula adherens (Latin for adhering spot) • Localized spot-like adhesions on the lateral or basal sides of plasma membrane • Link to intermediate filaments: in epithelial cells usually keratin in heart muscle desmin • Anchor proteins link between cadherins & intermediate filaments Roles: • Pin cells to each other or ECM • Give epithelia mechanical strength • Help to resist shearing forces Alberts 5th Ed: Fig 19-18 Desmosome structure Alberts 5th Ed: Fig 19-17 Communication Junctions: Gap Junctions A physical connection between two cells: connects the cytoplasm of cells • Each cell has one half channel (connexon) which connect across the intercellular space • Made of proteins call connexins which form a ring • When connexons on adjacent cells meet a channel forms between them Alberts 5th Ed: Fig 19-34 Communication Junctions: Gap Junctions A physical connection between two cells: connects the cytoplasm of cells Several connexons Alberts 5th Ed: Fig 19-35 Gap Junctions - Functions The channel between adjacent cells allows things to pass between them:Allows molecules <1,000 Da to pass through e.g. metabolites, inorganic ions, vitamins NOT macromolecules (proteins, RNA) Allows for chemical transmission between cells: small secondary messengers (Ca2+, cAMP & inositol triphosphate); coordination of responses Allows direct electrical transmission between cells e.g. in cardiac muscle the signal to contract rapidly transmitted through gap junctions allowing cells to contract in unison Almost all cells have gap junctions: exceptions include sperm cells & erythrocytes Summary: Cell junctions The various occluding & anchoring junctions work together to give the epithelium its physical properties Alberts 5th Ed: Fig 19-3 Learning outcomes: this lecture By the end of this lecture you should be able to:Recall the main types of cell junction (anchoring, tight & gap) & name the proteins that make up each For tight junctions: describe the arrangement of tight junctions between cells in an epithelial sheet, & explain how this seals the sheet to passage of substances For anchoring junctions: explain which junctions interact with which components of the cytoskeleton, & what properties this infers. Recall which junctions link cells to one another & which link cells to the ECM For gap junctions: sketch the structure of the connexon that links two cells together, & recall what substances can (and can’t) pass through it Sketch the typical arrangement of tight & anchoring junctions within an epithelial sheet Using your knowledge of their features, explain the key roles that each junction plays & give examples of tissues or organs where they are particularly important