Cells rely on specialized molecules called proteins to perform diverse functions, from accelerating chemical reactions to providing structural support. The cellular machinery responsible for constructing these protein molecules is the ribosome. Built from ribosomal RNA and proteins, ribosomes assemble amino acids into precise sequences based on genetic instructions.
The Two Populations of Ribosomes
Ribosomes exist in two distinct populations within a cell, differentiated by their location. Free ribosomes float within the cytoplasm, the jelly-like substance filling the cell. Bound ribosomes are attached to the outer surface of the endoplasmic reticulum, a network of membranes. Both free and bound ribosomes are structurally identical and interchangeable, able to switch between free or bound states depending on the protein being synthesized.
The Role of Free Ribosomes
Free ribosomes synthesize proteins that function within the cytoplasm or are transported to specific organelles not directly connected to the endomembrane system. Many enzymes for metabolic pathways, such as glycolysis, are produced by free ribosomes and remain in the cytoplasm. Structural proteins, like actin, which forms part of the cytoskeleton and provides shape and movement to the cell, are also synthesized by these ribosomes. Proteins imported into the nucleus, mitochondria, or peroxisomes are also synthesized on free ribosomes. Examples include nuclear proteins like histones, most mitochondrial proteins involved in cellular respiration, and peroxisomal enzymes for fatty acid breakdown. These are all made in the cytoplasm before being imported into their respective organelles.
Protein Synthesis by Bound Ribosomes
Bound ribosomes specialize in synthesizing proteins intended for three primary destinations: secretion outside the cell, insertion into cellular membranes, or delivery to specific organelles within the endomembrane system. Proteins destined for secretion, such as hormones like insulin, which regulates blood sugar, or antibodies, which are part of the immune response, are synthesized by ribosomes attached to the endoplasmic reticulum. These proteins typically move through the secretory pathway before being released from the cell. Other proteins produced by bound ribosomes become integral components of various cellular membranes, including the plasma membrane, endoplasmic reticulum, Golgi apparatus, and lysosomal membranes. Examples include channel proteins that allow substances to pass across membranes, or receptor proteins that bind to signaling molecules on the cell surface. These proteins are inserted directly into the membrane during their synthesis. Proteins destined for organelles like lysosomes, which are responsible for waste degradation within the cell, are also synthesized by bound ribosomes. These lysosomal enzymes are directed to their correct location through the endomembrane system.
The Signal Hypothesis: How a Ribosome Gets Its Assignment
The mechanism that determines whether a ribosome remains free or becomes bound to the endoplasmic reticulum is explained by the signal hypothesis, which can be thought of as a cellular “zip code” system. All protein synthesis begins on free ribosomes in the cytoplasm.
As the ribosome starts translating messenger RNA into a protein, the very first part of the newly forming protein is examined. If this initial segment contains a specific sequence of amino acids, known as a signal peptide, it acts like a shipping label, indicating the protein’s destination.
This signal peptide is recognized by a signal-recognition particle (SRP), which temporarily halts protein synthesis and directs the entire ribosome-mRNA-protein complex to the endoplasmic reticulum membrane. The complex then binds to a receptor on the ER, and the signal peptide inserts into a protein channel, allowing the ribosome to become “bound.” Protein synthesis then resumes, with the growing protein entering the ER lumen or embedding into the ER membrane. If the newly forming protein lacks this specific signal peptide, the signal-recognition particle does not interact with it, and the ribosome remains free in the cytoplasm, completing the protein’s synthesis there.