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CELL-CELL INTERACTION

Evy Sulistyoningrum

Introduction

Cells of multicellular organism communicate each other Coordinate integrated function Communication between cells: Releasing signal molecules Cells receptor protein specific Cell signaling: Autocrine signaling Direct contacts Paracrine signaling Endocrine signaling Synaptic signaling

Means of cell signaling

Speficity of cells receptor protein

Cells receptor protein

Intracellular receptor
Cytoplasm

or nuclear

receptor Lipid soluble signals Ex: steroid hormone, vitamin D, etc Mechanism of action:
Gene

regulators Enzymes

Cells receptor protein

Cell surface receptor Water soluble signals Converts extracellular to intracellular signals 3 class of cell surface receptors: Chemically gated ion channels Enzyme-linked receptors G-protein linked receptor Most abundant 7 trans-membrane protein linked with GTPbinding protein

Cells surface receptor

G-protein linked receptor

Second messengers

Second messengers : intracellular mediators Substances that relay receptors to target protein Most widely used: Cyclic adenosine monophosphate (cAMP) Produced by adenylil cyclase Calcium Stored in RE Calmodulin helps activated target protein

How 2nd messengers work?

Signal amplification

Low signals must be amplified to acquired adequate response Tyrosine kinases

Direct contacts

Direct contact between cells surfaces Cell junctions: long-lasting interactions/permanent contacts between cells Types of direct contacts:
Tight

junctions Anchoring junctions Communicating junctions

Direct contacts

Tight junctions

Occluding junctions: Zonula Occludens Connects plasma membrane of adjacent cells in a sheet Locate at the very apical end of junctional complexes between cells Functions:
Form

a selective permeability barrier across epithelial sheet Seals off body cavities such as intestine, stomach lumen, bile duct, blood-brain barrier, etc.

Tight junction

Structure of tight junction as a honeycomb-like network of ridges & grooves Linkage of rows of protein particles (3-4 nm ) Major proteins: occludin, claudin-1, JAM (junction adhesion molecule) Prevents the diffusion of macromolecules across epithelial sheet Prevents diffusion of membrane proteins and glycolipids between the apical and the basolateral regions of the plasma membrane

Lodish et al., 2004

Alberts et al., 2002

The role of tight junctions in allowing epithelia to serve as barriers to solute diffusion
Alberts et al., 2002

Anchoring junctions
Specialized region on the cell surface Contains cell-adhesion molecules or adhesion receptors that interact with other cells or the extracellular matrix and with cytoskeletal fibers Common in tissues exposed by mechanical stress, ex: muscle, skin Major types: Adherens junctions (zonula adherens) Desmosomes (macula adherens) Hemidesmosomes

Adherens Junctions
Also known as zonula adherens
A type of specialized adhesive junction, partially common in epithelia

Plasma membranes of adjacent cells are connected by cadherins or other cell adhesion molecules (e.g., integrins)

Alberts et al., 2002

Lodish et al., 2004

Alberts et al., 2002

Desmosome
macula adherens Disc-shaped adhesive junction (~1 mm diameter) Located basal to adherens junction Contains desmogleins & desmocollins (desmosomal cadherins) Found in variety of tissues (need mechanical strength: e.g., cardiac muscle & epithelia of skin and uterine cervix)

Desmosomes

Desmosome
Inner surface of plasma membrane: dense cytoplasmic plaques As site of anchorage for looping intermediate filaments that extend into the cytoplasm

contains desmoplakins & plakoglobin (adaptor proteins that link desmosomal cadherins to intermediate filaments ) 3-D network of intermediate filaments provides structural continuity and tensile strength to the entire sheet of cells
Pemphigus vulgaris : has antibody against one of his/her own desmogleins loss of epidermal cell-cell adhesion

Pemphigus vulgaris

Hemidesmosome
Half desmosome Specialized adhesive structure at the basal surface of epithelial cells

Function: attach the cells to their underlying basement membrane (basal lamina)
Contains a dense plaque on the inner membrane, with keratin-containing intermediate filaments coursing out into the cytoplasm

Lodish et al., 2004

a b

Karp, G., 2005

Communicating junctions

Passageways between cells that allow transfer of chemical or electrical signals Types:
Plasmodesmata:

plants Gap junctions: animal

Gap Junctions
Sites between animal cells that are specialized for intercellular communication Span the adjacent plasma membranes with very fine molecular pipelines that allow the passage of small molecules (1000 daltons) Electrical & metabolic couplings Regulation

pH: Low pH closes


Calcium: High calcium closes Extracellular signals: Dopamine closes

Gap junction
Gap junctions are constructed from transmembrane protein called connexin Six identical protein subunits assemble to form a structure called connexon

Two connexons from adjacent plasma membranes align to form a continuous aqueous channel of gap junction Gap junctions in different tissues can have different permeability due to difference in connexin (there are at least 11 distinct connexins)

Gap Junctions
Comprised of connexons

Connexons made of connexins

A summary of various cell junctions found in vertebrate epithelial cells


Alberts et al., 2002

Paracrine signaling

Signal molecules released by cells diffuse through the extracellular fluid to other cells Molecules are taken up by neighboring cells or quickly removed Influence is restricted to cells in the immediate vicinity of the releasing cell short-lived, local effects Early development, coordinating the activities of clusters of neighboring cells

Paracrine signaling

Endocrine signaling

Released signal molecule enter the organisms circulatory system travel widely throughout the body. Longer lived signal molecules May affect cells very distant from the releasing Cell Signal molecules: hormones Endocrine system

Endocrine signaling

Synaptic signaling

Cells of the nervous system provide rapid communication with distant cells. Signal molecules travel through long, fiberlike extensions of nerve cells from their tips very close to the target cells Signal molecules (neurotransmitters) The narrow gap between the two cells : chemical synapse Neurotransmitters cross the synapse and persist only briefly

Synaptic signaling

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