Cell Signalling

169

Cell signalling is the respond to extracellular signals produced by other cells or by themselves. This allows cell-cell communication and is necessary for the functional regulation and integration of multi-cellular organisms.

  • Signalling molecules are either secreted or expressed at the cell surface.
  • Signalling molecules can bind to receptors on the surface of another or the same cell.
  • Different type of signalling molecules transmit information in multi-cellular organisms, and their mechanisms of action on their cells can be diverse.
  • Some signalling molecules can act on the cell surface after binding to cell surface receptors; others can cross the plasma membrane and bind on intracellular receptors in the cytoplasm and nucleus.
  • When a signalling molecule binds to its receptor, it initiates a cascade of intracellular reactions to regulate critical functions such as cell proliferation, differentiation, movement, metabolism, and behaviour.
  • Because of their critical role in the control of normal cell growth and differentiation, signalling molecules have acquired significant relevance in cancer research.

Types of Cell Signalling

These are of five major types-

  1. Endocrine cell signalling
  • It involves a signalling molecule, called a hormone, secreted by an endocrine cell and transported through the circulation to act on distant target cells.
  • As an example is the steroid hormone testosterone produced in the testes that stimulate the development and maintenance of the male reproductive tract.
  1. Paracrine cell signalling
  • It is mediated by a signalling molecule acting locally to regulate the behaviour of a nearly cell.
  • An example is the action neurotransmitters produced by nerve cells and released at a synapse.
  1. Autocrine cell signalling
  • It is defined by cells responding to signalling molecules that they themselves produce.
  • A classic example is the response of cells of the immune system to foreign antigens or growth factors that trigger their own proliferation and differentiation.
  • Abnormal autocrine signalling leads to the unregulated growth of cancer cells.
  1. Neurotransmitter cell signalling
  • It is a specific form of paracrine signalling.
  1. Neuroendocriner cell signalling
  • A specific form of endocrine signalling.

Cell Signalling

Cell signalling molecules and their mechanism of action

  • These molecules exert their action after binding to receptors expressed by their target cells which can determine either a negative or positive feedback action which finally regulates the release of the targeting hormone.
  • Cell receptors can be expressed on the cell surface of the target cells.
  • Some receptors are intracellular proteins in the cytosol or the nucleus of target cells. Intracellular receptors require that the signalling molecules diffuse across the plasma membrane.
  • Steroid hormones belong to this class of signalling molecules. Steroid hormones are synthesized from cholesterol and include testosterone, estrogen, progesterone, and corticosteroids.
  • Testosterone, estrogen, and progesterone are sex steroids and are produced by the gonads.
  • Corticosteroids are produced by the cortex of the adrenal gland and include two major classes: glucocorticoids, which stimulate the production of glucose, and mineralocorticoids, which act on the kidney to regulate water and salt balance.
  • There are three cell signalling molecules that are structurally and functionally distinct from steroids but act on target cells by binding to intracellular receptors after entering the cell by diffusion across the plasma membrane.
  • They include thyroid hormone (produced in the thyroid gland to regulate development and metabolism), Vitamin D (regulates calcium metabolism and bone growth), and retinoids (synthesized from vitamin A to regulate development).
  • Steroid receptors are known to be members of the steroid receptor superfamily. They function as transcription factors by their DNA binding domains that consist of transcription activation or repression functions.
  • Steroid hormones and related molecules can, therefore, regulate gene expression. In the androgen insensitivity syndrome (also known as the testicular feminization syndrome [T fm]) there is a mutation in the gene expressing the testosterone receptor such that the receptor cannot bind the hormone, and hence the cells do not respond to the hormone.
  • The individual develops the secondary sexual characteristics of a female although genetically male.
  • Nitric oxide is also a signalling molecule. It is a simple gas which is synthesized from the amino acid arginine by the enzyme nitric oxide synthase. It functions as a paracrine signalling molecule in the nervous, immune, and circulatory systems.
  • Nitric oxide can diffuse across the cell membrane of its target cells like steroid hormones,
  • Nitric oxide does not bind to an intracellular receptor to regulate transcription like the steroids rather it regulates the function of intracellular target enzymes.
  • Nitric oxide escalates the function of the second messenger cyclic guanosine monophosphate in smooth muscle cells, which ultimately causes cell muscle relaxation and blood vessel dilation.
  • Nitroglycerin which is a pharmacologic agent used in the treatment of heart disease is converted to nitric oxide, which increases heart blood flow by dilation of the coronary blood vessels.