Receptors and junctions
Cell communication in Eukaryotes is very involved. Many sorts of cell junctions are used for various purposes. The non-communicating junctions are 'simple' adhesion structures: they do not allow passage of anything from one cell to another. They include:
- Tight junctions bind cells tightly together with claudin proteins. This sort of junction is common in epithelial cells, where is serves to strictly compartmentalise an external compartment (lumen of bowel) from an internal compartment (coelom).
- Adhesion belts, which use cadherin proteins to glue cells together.
- Desmosomes, which are adhesion belts connected to the intermediate fibres of the cytoskeleton.
- Integrins, selectins and CAMs (immunoglobulin-like adhesion molecules) generally occur singly, and provide a mechanism for cell-cell recognition.
Cells also adhere to the extracellular matrix by similar means:
- Hemidesmosomes bind the ECM to intermediate filaments via integrins.
- Focal adhesions bind the ECM to actin microfilaments via integrins and help promote cell survival through focal adhesion kinase.
- Single integrins and proteoglycans (particularly those containing heparan sulfate) also bind the ECM.
Communicating junctions on the other hand, do allow things to move from one cell to another. They include:
- Synapses (allow chemical connection between nerve cells. Transduce electrical into chemical signals).
- Gap junctions, formed by connexin proteins, which allow electrical and some solute communication as well as anchoring cells together.
- Plasmodesmata (between SERs in plants).
The distance involved in junctions can also be used to classify the types of communication possible.
- Autocrine (same cell).
- Synaptic (one cell immediately in contact).
- Tethered (one cell in immediate contact, but non-mobile ligand).
- Paracrine (nearby cell, community coherence, neuromodulation).
- Endocrine (hormonal, action-at-a-distance).
- Pheromonal (different organism).
For cells to communicate, there must be a receptor and a ligand. Receptors in eukaryotes fall into several huge and diverse families. The immunoglobulin superfamily contains the immunoglobulins, T-cell receptors, many other immune-system receptors, and even some growth factors. Some examples:
- Immunoglobulin-E (IgE) is involved in inflammatory responses, principally against parasitic worms, but lately, also in allergies: when IgE interacts with an allergen, bound to a mast cell, it crosslinks two IgE molecules together, leading to a signal cascade that eventually causes histamine release from the cell. Histamine causes the symptoms of allergy and inflammation, which allows more immune cells to get to the affected site.
- T-cell receptor (TCR) and antigen presenting cell (APC) interactions. An APC bears one of the immunoglobulin-like major histocompatibility complex proteins (MHC) on its surface, which bears antigenic peptides from potential pathogens. TCRs interact with these APCs: if the antigen is recognised as 'non-self' the T cell will be sent on its murderous way to attack the bearer of the antigen.
- TCR and MHCII (vesicular/viral digests) binding is stabilised by CD-4, another immunoglobulin-like molecule. HIV specifically targets and kills CD-4 bearing immune cells.
- TCR and MHCI (cytosolic digests) stabilised by CD-8.
- FGF (fibroblast growth factor), PDGF (platelet derived) and NGF (nerve) are immunoglobulin-like growth factors. The TCR is also a growth factor of sorts, as its activation makes the T-cell proliferate.
The G-protein coupled (GPC) receptors are another ubiquitous group. A GPC receptor hat has bound its ligand activates a G-protein, which binds GTP. The alpha subunit of the G-protein dissociates from the beta-gamma subunit of the G-protein, and this activates a second messenger. This may be one of:
- Adenylate cyclase, making cAMP. cAMP binds PKA (protein kinase-A), whose activity regulates other proteins.
- Phospholipase-C (PLC). PLC yields diacylglycerol (DAG) and inositol triphosphate (IP3) from phophoinositol. IP3 releases calcium from the SER, which causes calmodulin to bind CAM-KII, a kinase. Calcium and DAG also activate protein kinase-C (PKC).
Ion channels are a third superfamily of receptors. They are 'gated' in some way, i.e. they respond to a particular cue that causes them to open. They may be:
- Mechanically gated, responding to stretching, as in the statolith receptors in plant roots.
- Voltage gated: voltage gated sodium channels in the neuron allows sodium in, depolarising the membrane.
- Ligand gated ion channels are found in photoreceptors: an action potential is generated by the efflux of ions gated by a chemical released when the photoreceptor is irradiated.
Steroidal receptors are unusual in that they are not membrane bound. They reside in the nucleus itself, as steroids are sufficiently hydrophobic to enter the cell directly by diffusion through the membrane. The steroidal ligand binds an inhibitor protein, which frees the receptor to bind DNA as a dimer and activate protein synthesis.
Leucine rich repeat receptors are important in plant recognition of, and resistance to, pathogens.
Tyrosine kinase receptors are one of the most diverse groups. The insulin receptor (a cystine rich dimer) and EGF (epidermal growth factor) receptors are both tyrosine kinases. Both are transmembrane proteins that have a ligand binding domain on the outside of the cell, and a kinase domain on the inside. In the EGF receptor, the ligand (EGF) causes dimerisation and autophosphorylation of the receptor. This sets off a signal cascade: the activated receptor binds a protein called grb-2, which itself binds SOS, which then binds Ras-GTP or Raf. These last two set off the MAPKKK (mitosis activation protein kinase kinase kinase) chain: MAPKKK phosphorylates MAPKK, which phosphorylates MAPK, which phosphorylates MAP. MAP phosphorylates a transcription factor called c-Jun, which recruits RNA polymerase and starts the transcription of genes involved in mitosis. At each stage down the chain of kinases, we get amplification of the original signal, so the cell can respond to very little EGF.
The ligands of receptors are also grouped into several families. Many are fatty acid derivatives: both the prostaglandins of mammals (aspirin blocks this pathway, which is involved in inflammation) and jasmonic acid (involved in plant resistance to insects) are fatty acid derivatives. The plant growth hormone cytokinin is an nucleotide derivative. Amino acid derivatives (waste products indicate an active cell?) are also common:
- Histamine (histidine derivative: blood vessels become leaky, and cause inflammation).
- Dopamine (tyrosine derivative: Parkinson's disease is caused by faulty dopamine metabolism; it is also the pathway cocaine interferes with).
- Glycine (inhibitory synapses).
- Glutamate (stimulatory in insect synapse).
- Acetylcholine (muscle contraction).
- Serotonin (tryptophan derivative: LSD mimics serotonin, Prozac decreases its degradation, and MDMA (ecstasy) increases its production).
- Adrenaline and noradrenaline (flight-or-fight responses, also a neurotransmitter).
- Thyroxine (growth hormone containing iodine).
- Auxin (tryptophan derivative: in plants it causes branchy roots and unbranched shoots. Agent Orange over activates the receptors, causing uncontrolled growth and death).
The most diverse group of ligands are the peptides and proteins. These include the enkephalins (endorphins, whose interactions morphine interferes with), vasopressin (mammalian diuresis), systemin (plant resistance to insects). The larger proteins include insulin and glucagon (control of mammalian blood sugar), somatotrophin (an insulin-like growth factor), lutropin, follitropin and gonadotrophin (sexual cycles in placental mammals), and the EGF and NGF growth factors.
The steroids are part of a larger group of terpene derivatives. The true steroids include cortisol (a human stress hormone), and the human sex hormones progesterone, estradiol and testosterone. The other terpenoids are more common in plants: abscisin is responsible for plant dormancy responses, and shuts guard cells during drought, and gibberellin is a plant growth hormone that can be exploited to cause parthenocarpy, i.e. seedless fruits.
Finally, some of the other ligands are a little harder to classify. Salicylic acid is a plant hormone involved in activating the alternative oxidase, which warms the insect-attracting smelly spadix of aroids. It is also involved in plant resistance to fungi. Ethene is probably the most unusual hormone of all: it's a gas involved in stress and senescence responses in plants. The compound Etherel is a ethene precursor, and is used to ripen bananas that have been harvested green to increase their portability.
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