L16 - Polarity

what is the establishment of apical basolateral polarity important for?

• cell form and cell function

what does cell polarity generate?

a wide variety of forms which allows a diverse array of functions

what is cell polarity?

the asymmetric organisation of cell

• where different parts of the cell have different structures and functions

what is the key feature of cell polarity?

• components are unevenly distributed across the plasma membrane and inside the cell

• this creates distinct regions with specific compositions and functions - allowing different capabilities, morphologies and functions

what does polarity determine?

how cells divide and specialise

what are the two main routes to generate diversity?

1. asymmetric division

2. symmetric division

asymmetric division

• polar mother cell divides to generate daughters that have inherited different components

symmetric division

daughters initially identical but exposure to different environmental cues causes them to become different

what are the two model organisms used to study cell fate decisions?

• C. elegans

• Drosophila

why were C. elegans and Drosophila used to study cell fate decisions?

because they are relatively simple organisms making it easier to follow cell fate and understand how polarity contributes to cell fate

what did studies in C. elegans (worm) help understand?

• mechanisms important in cell polarisation

• particular lineages arise after various asymmetric divisions within the C. elegans embryo

• allowed to identify the proteins essential for polarisation in the embryo

what did the genetic screen in C. elegans identify?

• key genes called par genes which control asymmetric cell division

• molecular machinery = par genes + their proteins

par genes

• crucial for establishing and maintaining cell polarity

• control asymmetric cell division

• genes deficient in partition

• the par genes encode the par proteins

• par 1-6 and atypical protein kinase C (aPKC)

what are par mutants?

• mutated par genes

• causing cells to lose polarity

• cells divide symmetrically (identical) instead of asymmetrically (different)

  —> which is bad because asymmetric divisions are needed to create different tissues and body axes

what is the polarity in embryo established by?

1. symmetry breaking

2. establishment of polarity

3. maintenance of polarity

how is polarity between the anterior and posterior pole mediated?

by Par protein complexes - through a negative feedback mechanism

• these complexes prevent the proteins at one end of the cell going to the other proteins on the other end (through phosphorylation)

• this is done by the par protein = protein kinase C

• the protein kinase C phosphorylates proteins preventing them from going into the wrong domain

how are the par proteins central to cell polarity networks?

• the par proteins help set up opposing membrane domains (apical vs basolateral)

• this network works through mutual antagonism - each domain excludes the proteins from the other

• this defines the cell’s polarity axis

what do the par proteins rely on in order to maintain the polarity?

the cytoskeleton

why is the cytoskeleton key to maintain cell polarity?

• the actin filaments and microtubules provide structure and dynamic control to maintain polarity

what does the cytoskeleton connect to?

junctional proteins

what do the cell junctions do?

• help establish and maintain polarity by interacting with the cytoskeleton

what are the 6 cell junctions that establish polarity through interaction with the cytoskeleton?

1. tight junctions

2. adherens junctions

3. gap junctions

4. desmosomes

5. hemidesmosomes

6. actin-linked cell-matrix junction

tight junctions

seal gaps between epithelial cells

aherens junction

connect actin filament bundle in one cell with that in the next cell

desmosomes

connects intermediate filaments in one cell to those in the next cell

gap junction

allows the passage of small water soluble molecules from cell to cell

hemidesmosomes

anchors intermediate filaments in a cell to extracellular matrix

actin linked cell matrix junction

anchors actin filaments in a cell to the extracellular matrix

what do integrins do?

• they form a bridge between the cytoskeleton and the ECM

• allowing for structural support and signalling across membranes

what are junctions important for?

act as permeability barrier

• they control what can pass between cells in a tissue

what are cadherins?

• family of cell adhesion proteins that help cells stick to each other (cell-cell adhesion)

• important for tissue organisation

• low affinity interactions but there’s many of them so they contribute to high level of interaction

what does maintenance of cell polarity depend on?

1. endocytosis

2. secretion

3. recycling

what does vesicle trafficking contribute to?

establishment of polarity

what does transcellular transport of glucose rely on?

cell polarisation

what are the two main example where polarity is important physiologically?

1. shaping - development and tissue remodelling

2. cancer

explain how polarity is important in shaping - during development and tissue remodelling

• when an epithelial layer needs to invaginate to form a tube during development there’s a tightening of the adhesion belt

• this tightening allows invagination to occur

• the epithelial sheet curves inwards and pinches off from the overlying sheet of cells

• forming the epithelial tube

explain how polarity is important in cancer

• if polarity is lost

• cell lose their apical-basal orientation

• causing the cells to divide inappropriately and detach from their neighbours and promote invasion into surrounding tissue

loss of polarity = motile invasive cells = metastasis

what does it mean cell polarity is highly dynamic?

means its actively maintained and remodelled allowing cells to be flexible while staying organised

what does interference with membrane trafficking disrupt?

cell polarity → loss of polarity → malignancy (cancerous tumour)

what happens to cells in epithelial to mesenchymal transition?

epithelial cells lose polarity and gain migratory invasive mesenchymal features which enables metastasis