Harris Lecture 3 notes (1 per page)(1)-1

Harris Lecture 3 notes (1 per page)(1)-1 - Cell-cell...

Info iconThis preview shows page 1. Sign up to view the full content.

View Full Document Right Arrow Icon
This is the end of the preview. Sign up to access the rest of the document.

Unformatted text preview: Cell-cell adhesion How can small and fragile cells form large and stable organisms? ? 1 1 Cells are organized into one of two main tissue categories (these support the animal body plan) actin network provide resistance to mechanical stress migratory, single cell Epithelial tissues Connective tissues cells directly connected with > cells dispersed with > Epithelial tissues has minimal ECM beneathe ECM provides the overall structure of connective tissue. 2 2 Why is epithelial structure important? More than 60% of the cell types in the vertebrate body are epithelial. Epithelia form our skin and coat our organs. Connective tissue cells include muscle cells, neurons and immune cells. 3 3 Epithelia form our skin and coat our internal organs Schematic Cross Section of the Human Abdomen (inds.co.uk) MBoC 4th Ed. Epithelia are critical for organ structure and function 4 4 Epithelial structure and function requires junctional complexes tight junction seals the gap between 2 cells 5 5 Adherens junction structure Adherens junctions can form strong continuous adhesion belts critical for adhering cells to form epithelia Adherens junctions connect actin bundles in 1 cell with actin bundles in cells around it. circle of actin bundle no separation between membranes even spacing between membranes darker materials are the cytoskelet 6 6 Adherens junction structure Adherens junctions can form strong continuous adhesion belts critical for adhering cells to form epithelia Cadherin clusters mediate the adhesion one cell Cadherin cluster another cell 7 7 Adherens junction structure Cadherin clusters mediate the adhesion through: homophilic interactions between cadherin receptors 1. > 2. Links to the actin cytoskeleton caherin on 1 cell likes to bind to the same kind of caherin on another cell 5 individually folded domain adapter proteins The overall structure is supported by Ca2+. 8 8 Adherens junction function: Tissue maintenance during development Adherens junctions are not static. It's changing shape, breaking connections with some cells, and making new contacts with others. Movement of the outer epithelium of the Drosophila embryo 9 9 Adherens junction function: Tissue maintenance during development Tissue structure is lost in adherens junction mutants 10 10 Adherens junction function: Tumour suppression stratified epithelium • The loss of epithelial structure is a hallmark of cancer • Cadherins are tumour suppressors hold cells together 11 11 Why is epithelial structure important? Epithelia have distinct apical and basal sides -the apical surface faces > organ lumen or animal surface, outside -the basal surface faces > connective tissue This epithelial polarity of critical for organ function apical and basal faces are different. 12 MBC@NCBI 12 e.g. Epithelial polarity controls solute diffusion between our body compartments sugar importer e.g. Controlling glucose transport into the blood The glucose is blocked from diffusing between cells by tight junctions Instead, it must be actively transported through cells by plasma membrane channels allowing for precise regulation. How are the channels positioned? sugar exporter What would happen without tight junctions? 13 13 e.g. Epithelial polarity controls solute diffusion between our body compartments e.g. Controlling glucose transport into the blood The glucose is blocked from diffusing between cells by tight junctions Instead, it must be actively transported through cells by plasma membrane channels allowing for precise regulation. How are the channels positioned? What would happen without tight junctions? 14 14 Testing the permeability barrier across an epithelia (a) (b) If a dye was added below an epithelium with tight junctions how far could it diffuse? (c) 15 15 Testing the permeability barrier across an epithelia added apically or basally? added apically or basally? Tracer molecule (black) added to apical or basal side of the epithelium What would happen without tight junctions? 16 16 Tight junctions encircle the apical end of each cell in an epithelial sheet Basal Apical 17 17 Tight junctions are formed from strands of interacting transmembrane proteins multiple layers of the seal apical 18 18 Tight junctions are formed from strands of interacting transmembrane proteins Core tight junction proteins: Claudin making the strands • 4-pass transmembrane protein • essential for > tight junction formation Occludin making the strands SEAL • 4-pass transmembrane receptor • required for > barrier function • not needed for maintaining 19 overall tight junction structure 19 Tight junctions function as… “gates” to prevent molecular movement across the epithelial sheet in the > EC space between cells “fences” to prevent molecular movement between the apical and basolateral domains of > each cell's plasma membrane 20 20 Cell Polarity is Fundamental to Cell and Developmental Biology neurons 21 animal embryo plant embryo amoeboid cell 21 How is cell polarity first established? How is it further elaborated? How is cell polarity linked to other cellular machinery? 22 22 In general, cells use ‘landmarks’ to establish and elaborate polarity Primary recruit other things Landmark Subsequent Elaboration 23 23 In C. elegans, sperm entry provides a landmark for polarizing the one-cell embryo asymmetry cue Sperm Entry Cytoskeletal Flow Anterior Posterior 24 24 In C. elegans, sperm entry provides a landmark for polarizing the one-cell embryo flow of actin and myosin to the anterior Cytoskeletal Flow Anterior Cues Anterior Posterior 25 25 In C. elegans, sperm entry provides a landmark for polarizing the one-cell embryo mutually exclusive some are cell fate determinant Anterior Cues Anterior divide in the middle Posterior Cues Posterior 26 26 Adherens junctions (AJs) are important landmarks for epithelial polarity Lumen or Exterior Space Apical Domain AJs Basolateral Domain Underlying Tissue 27 27 actin based protrusion cell looking for neighbours Contacts between cell protrusions form landmarks for AJ assembly between mammalian cells in culture Adherens junction start to form. AJs 28 Cynthia L. Adams, W. James Nelson, and Stephen J Smith (1996) 28 Contacts between cell protrusions form landmarks for AJ assembly between mammalian cells in culture Actin protrusions Diffuse AJ components AJs AJ puncta small clusters of cadherins. 29 Cynthia L. Adams, W. James Nelson, and Stephen J Smith (1996) 29 Contacts between cell protrusions form landmarks for AJ assembly between mammalian cells in culture Actin protrusions Diffuse AJ components AJ puncta Modified actin structure Continuous AJs The cell will have continuous AJ all around this cell. AJs 30 Cynthia L. Adams, W. James Nelson, and Stephen J Smith (1996) 30 a sheet of cells Contacts between cell protrusions form landmarks for AJ assembly between mammalian cells in culture Actin protrusions Diffuse AJ components AJ puncta Modified actin structure Mesenchymal-to-epithelial transition Epithelial to mesenchymal is cancer AJs Continuous AJs 31 Cynthia L. Adams, W. James Nelson, and Stephen J Smith (1996) 31 Adherens junctions (AJs) also act as landmarks to elaborate epithelial polarity Cadherin Cadherin Arm Cadherin -cat -a c F t in Apical Domain Basolateral Domain 32 32 Adherens junctions (AJs) also act as landmarks to elaborate epithelial polarity Apical Cues Cadherin Arm -cat F -a t in c Basal Cues 33 33 Conserved apical and basal cues controlling epithelial polarity 34 34 The integration of polarity complexes, adhesion complexes, cytoskeletal networks and trafficking routes is critical for the structure and function of epithelia that form our organs Complexes required for epithelial structure A functional epithelium Body compartments constructed from functional epithelia 35 35 Lecture 3 reading 1131-1139 (not figures 19-6 or 19-7 or table 19-3) figure 19-14 1150-1153 1155-1157 36 36 ...
View Full Document

This note was uploaded on 04/03/2012 for the course BIOLOGY BIO230 taught by Professor Harris during the Fall '11 term at University of Toronto- Toronto.

Ask a homework question - tutors are online