9.1 Signaling Molecules and Cellular Receptors

Cells communicate by both inter- and intracellular signaling. Signaling cells secrete ligands that bind to target cells and initiate a chain of events within the target cell. The four categories of signaling in multicellular organisms are paracrine signaling, endocrine signaling, autocrine signaling, and direct signaling across gap junctions. Paracrine signaling takes place over short distances. Endocrine signals are carried long distances through the bloodstream by hormones, and autocrine signals are received by the same cell that sent the signal or other nearby cells of the same kind. Gap junctions allow small molecules, including signaling molecules, to flow between neighboring cells.

Internal receptors are found in the cell cytoplasm. Here, they bind ligand molecules that cross the plasma membrane; these receptor-ligand complexes move to the nucleus and interact directly with cellular DNA. Cell-surface receptors transmit a signal from outside the cell to the cytoplasm. Ion channel-linked receptors, when bound to their ligands, form a pore through the plasma membrane through which certain ions can pass. G-protein-linked receptors interact with a G-protein on the cytoplasmic side of the plasma membrane, promoting the exchange of bound GDP for GTP and interacting with other enzymes or ion channels to transmit a signal. Enzyme-linked receptors transmit a signal from outside the cell to an intracellular domain of a membrane-bound enzyme. Ligand binding causes activation of the enzyme. Small hydrophobic ligands (like steroids) are able to penetrate the plasma membrane and bind to internal receptors. Water-soluble hydrophilic ligands are unable to pass through the membrane; instead, they bind to cell-surface receptors, which transmit the signal to the inside of the cell.

9.2 Propagation of the Signal

Ligand binding to the receptor allows for signal transduction through the cell. The chain of events that conveys the signal through the cell is called a signaling pathway or cascade. Signaling pathways are often very complex because of the interplay between different proteins. A major component of cell signaling cascades is the phosphorylation of molecules by enzymes known as kinases. Phosphorylation adds a phosphate group to serine, threonine, and tyrosine residues in a protein, changing their shapes, and activating or inactivating the protein. Small molecules like nucleotides can also be phosphorylated. Second messengers are small, non-protein molecules that are used to transmit a signal within a cell. Some examples of second messengers are calcium ions (Ca²⁺), cyclic AMP (cAMP), diacylglycerol (DAG), and inositol triphosphate (IP₃).

9.3 Response to the Signal

The initiation of a signaling pathway is a response to external stimuli. This response can take many different forms, including protein synthesis, a change in the cell’s metabolism, cell growth, or even cell death. Many pathways influence the cell by initiating gene expression, and the methods utilized are quite numerous. Some pathways activate enzymes that interact with DNA transcription factors. Others modify proteins and induce them to change their location in the cell. Depending on the status of the organism, cells can respond by storing energy as glycogen or fat, or making it available in the form of glucose. A signal transduction pathway allows muscle cells to respond to immediate requirements for energy in the form of glucose. Cell growth is almost always stimulated by external signals called growth factors. Uncontrolled cell growth leads to cancer, and mutations in the genes encoding protein components of signaling pathways are often found in tumor cells. Programmed cell death, or apoptosis, is important for removing damaged or unnecessary cells. The use of cellular signaling to organize the dismantling of a cell ensures that harmful molecules from the cytoplasm are not released into the spaces between cells, as they are in uncontrolled death, necrosis. Apoptosis also ensures the efficient recycling of the components of the dead cell. Termination of the cellular signaling cascade is very important so that the response to a signal is appropriate in both timing and intensity. Degradation of signaling molecules and dephosphorylation of phosphorylated intermediates of the pathway by phosphatases are two ways to terminate signals within the cell.

9.4 Signaling in Single-Celled Organisms

Yeasts and multicellular organisms have similar signaling mechanisms. Yeasts use cell-surface receptors and signaling cascades to communicate information on mating with other yeast cells. The signaling molecule secreted by yeasts is called mating factor.

Bacterial signaling is called quorum sensing. Bacteria secrete signaling molecules called autoinducers that are either small, hydrophobic molecules or peptide-based signals. The hydrophobic autoinducers, such as AHL, bind transcription factors and directly affect gene expression. The peptide-based molecules bind kinases and initiate signaling cascades in the cells.