Question

Cell Biology Tutorial: Introduction to Cell Integration and Adhesion

Answer 1

This is a tutorial, not a question. Although I appreciate any attempts to help, this is meant to be an educational resource. I will be handing out warnings and possibly suspensions for irrelevant spam comments.

Answer 2

\({\bf{Terminology:}}\)

-five types of cell tissue: epithelial, connective, muscular, neural, and blood
- epithelia: layer of cells which may serve as a permeable barrier or as a surface among other functions
- cell-adhesion molecules (CAM): membrane proteins that facilitate the adhesion of cells
> cadhreins
> immunoglobins
> integrins
> selectins
> can be homotypic/heterotypic: (binds cells of the same type)
> can be homophilic/heterophilic: binds the same kind of CAM/different kinds of CAMs
> can be cis/trans: interacts with other CAMs within the same membrane/interacts with CAMs on an adjacent cell membrane
> cis interactions also called intracellular/lateral
> trans interactions also called intercellular/adhesive

- adhesion receptors: bind cells to the ECM
- adapter proteins: bind CAMs to the cytoskeleton

\({\bf{The~ECM:}}\)

- extracellular matrix: network of proteins and polysaccharides
components:
> proteoglycan (perlecan)
> collagens: Type IV is sheet forming, types I/II/III are fibrillar
> multi-adhesive matrix proteins: laminin, fibronectin, nidogen/entactin

- functions of the ECM:
> anchoring cells
> determining chemical/physical properties
> controlling polarity/differentiation/and other elements of cell development
> cell migration
> growth facttor binding/reservation
> ligand in proteolytic cleavage
> mechanotransduction: converting biochemical process into or from a mechanical force

Answer 3

\({\bf{Epithelial~Organization:}}\)
- basic terminology: apical = top, lateral = side, basal = bottom, basolateral = combination of basal and lateral surfaces that have similar properties
- subtypes: simple columnar, simple squamous (scale-like, or thin/flattened cells), transitional, and stratified squamous
> simple columnar: unilayer of long cells, secretion/absorption, ex. GI cells
> simple squamous: thin cells, ex. blood vessels
> transitional: multiplayers of differently shaped/sized cells, expansion/contraction, ex: bladder
> stratified squamous: resistance of abrasion and barrier against absorption/secretion, ex. lining of the mouth

\({\bf{Overview~of~Junctions:}}\) anchoring, tight, gap
anchoring:
_ adherens junctions (CAM/adhesion receptor = cadherins)
- desmosomes (CAM/adhesion receptor = desmosomal cadherins)
- hemidesmosomes (CAM/adhesion receptor = integrins)
- focal/fibrillar/3D (CAM/adhesion receptor = integrins)

- tight: (CAM/adhesion receptor = occludin/claudin/JAM)
- gap: (connexins, innexins, pannexins)

Note: I will not be covering plasmodesmata (a type of junction found on plant cells) in this tutorial

Answer 4

\({\bf{Anchoring~Junctions:}}\)

Adherens Junctions and Desmosomes:
- primary CAM = cadherins

> classical cadherins: E,N,P (epithelial, neural, placental). E-cadherin is mostly homophilic
- transmembrane domain with C-terminal cytosolic domain + 5 cadherin domains EC1-EC5
- activity is dependent on Ca2+ binding for elongation and curvature

> demosomal cadherins: desmoglein and desmocollin; bind to adaptor proteins (plakoglobin + plankophilins forming desmosome plaques

> activity is dependent on Ca2+
- MDK cells show that E-cadherin is involved in attachment and sheet formation

Hemidesmosomes:
- primary CAM = integrins (alpha 6 beta 4), low affinity for substrate
> two types: RGD motif (arg-gly-asp sequence) and I-domain binding
> requires binding of divalent cations
- link adapter proteins to filaments

Answer 5

\({\bf{Tight~Junctions:}}\)
- restrict movement of solutes
- located in a band under the apical surface, surrounds the whole cell
- primary integral membrane proteins: occludin and claudin, also JAM (junction adhesion molecule) but less common
> occludin/claudin: 4 transmembrane helices often forming helix bundles and loops
> JAMs: single transmembrane domain + two extracellular immunoglobin domains
- C- terminal end binds to PDX domains which facilitate binding to C-termini of membrane proteins

Ways around tight junctions:
- paracellular pathway: uptake of molecules through certain parts of tight junctions
- transcellular pathway: uptake of molecules through the cell, avoiding the junction

\({\bf{Gap~Junctions:}}\)
- primary CAM: connexins
- allows small molecules to pass through (<1200 Da), ex second messenger
- selectivity is regulated by modifications of connexins; pH and Ca2+ sensitive
- innexins: present in invertebrates
- pannexins: both vertebrates and invertebrates; forms pannexons which are involved in ATP release/exchange