Cell-Cell Communication In Multicellular Organisms

Multicellular Organisms Require Cell-Cell Interactions Volvox, an algae Evolution of multicellularity

Cell-Cell Adhesion Defines Multicellularity The first traces of life appear nearly 3.5 billion years ago, in the early Archaean. Clearly identifiable fossils remain rare until the late Archaean, when stromatolites, layered mounds produced by the growth of microbial mats, become common in the rock record.

Caulobacter crescentus

Saccharomyces cerevisiae (G. Fink) More Complex Multicellular Organisms have Specialized Cell Types

Cells Can Interact With Each Other Indirectly Through Protein-based Scaffolds

Microbial Mats = Biofilms Attachment of a bacterium to a surface, or substratum, is the initial step in the formation of a biofilm Cell-surface adhesins that mediate contact with the host matrix The maturation of a biofilm community and their architecture can vary from flat, homogenous biofilms, to highly structured biofilms, connection between quorum sensing and biofilm formation Bacterial and fungal pathogens form biofilms

Microbial Mats = Biofilms Hypothetical signal gradients in a biofilm system. This schematic represents a side-view of (a) a flat and (b) a structured biofilm (s = substratum). This diagram represents speculation regarding potential signal gradients (indicated by the gray scale), with higher signal concentrations indicated by darker coloration. Factors, such as diffusion constants for the signal, mass transfer and non-uniform signal production, within different regions of the biofilm could all affect signal gradients. The two micrographs at the right of the figure represent side-views of confocal micrographs of P. aeruginosa PAO1 forming a flat and a structured biofilm.

Quorum Sensing Bacteria and Fungal Species Communicate By Sending and Receiving Chemical Signals the accumulation of signaling molecules enable a single cell to sense the number of bacteria (cell density). The marine bioluminescent bacteria Vibrio fischeri was grown in liquid cultures and it was observed that the cultures produced light only when large numbers of bacteria were present (Greenberg, 1997).

Quorum Sensing An Australian pinecone fish (12 cm long). The red organ on the lower jaw is a light organ that contains V. fischeri cells per ml fluid. Australian pinecone fish are nocturnal reef dwellers and they use the light organ to search for prey at night. A Hawaiian bobtail squid. This adult squid is 2 cm long. There is a V. fischeri light organ close to the ink sac within the mantle cavity of the animal. This light organ contains V. fischeri cells per ml. These nocturnal squid emit light downwards through the mantle cavity and, by matching the intensity of the moon- and starlight above, they become invisible to predators below them.

Quorum Sensing The lux operon contains luxI followed by five genes that are required for light production (luxCDABE) and an additional gene of unknown function (luxG). The luxC, luxD and luxE genes code for components of an acid reductase that converts the long-chain fatty acid tetradecanoic acid into the fatty-aldehyde substrate (tetradecanal) for the light-producing enzyme luciferase. The luxA and luxB genes encode subunits of luciferase. The luxI gene encodes the enzyme (autoinducer (AI) acyl-homoserine lactone synthase) that produces the quorum-sensing signal 3-oxo-C6-HSL. The single gene transcribed in the opposite direction, luxR, encodes the signal-responsive transcription activator of the lux operon.

Quorum Sensing

Model of acyl-homoserine-lactone (acyl-HSL) quorum sensing in a bacterial cell. Tentative mechanisms for acyl-HSL synthesis and acyl-HSL interaction with LuxR-type proteins are shown. Double arrows with filled yellow circles at the cell envelope indicate the potential two-way diffusion of acyl-HSLs into and out of the cell. The proposed dimerization of LuxR (red) is based on genetic evidence and biochemical analysis of TraR; other LuxR-type proteins might form higher-order multimers.

All C.elegans cells Are Formed in a Defined Program (959 somatic)

Cells Stick Together by Tight Junctions Prevent Membrane Protein and Lipid Diffusion

Desmosomes Are Button-Like Points of Intercellular Contact that Rivet Cells Together

GAP Junctions

Examples of Cell Adhesion Molecules 30nM

Integrins are Matrix Receptors Bind ligand with low affinity More of them on the cell surface Allowing Cell Separation from the Matrix 8 integrins bind fibronectin

Inside-out signaling

focal adhesion kinase (FAK) in mediates signals from the extracellular matrix through integrin receptors. FAK and its interacting partners play a central role in propagating signals that regulate cell motility.

Non-adherent cells undergo programmed cell death: Apoptosis -double stranded DNA cleavage 1-2 breaks can cause a cell cycle checkpoint -asymmetry lost in PM Phosphatidyl serine becomes exposed to WBC -caspase production Proteases that are themselves activated by cleavage Proteolytic cascade -pores in the mitochondria Involved in procaspase activation

Growth Factors and DNA damage can cause apoptosis

Bloom and Cross Nature Reviews Molecular Cell Biology 8, 149–160 (February 2007) | doi: /nrm2105