Protein Secretion

Most proteins synthesized by a cell remain in the cell, providing structure and function for the cell's survival. Some proteins, however, are secreted into the extracellular fluid, where they act as signals to other cells or provide material for forming the extracellular matrix to which tissue cells are anchored. Since proteins are large, charged molecules that cannot diffuse through cell membranes (as will be described in more

Vander et al.: Human Physiology: The Mechanism of Body Function, Eighth Edition

Genetic Information and Protein Synthesis CHAPTER FIVE

Genetic Information and Protein Synthesis CHAPTER FIVE

TABLE 5-2 Factors that Alter the Amount and Activity of Specific Cell Proteins

Process Altered

Mechanism of Alteration

1.

Transcription of DNA

Activation or inhibition by transcription factors

2.

Splicing of RNA

Activity of enzymes in spliceosome

3.

mRNA degradation

Activity of RNAase

4.

Translation of mRNA

Activity of initiating factors on ribosomes

5.

Protein degradation

Activity of proteosomes

6.

Allosteric and covalent modulation

Signal ligands, protein kinases, and phosphatases

detail in Chapter 6), special mechanisms are required to insert them into or move them through membranes.

Proteins destined to be secreted from a cell or become integral membrane proteins are recognized during the early stages of protein synthesis. For such proteins, the first 15 to 30 amino acids that emerge from the surface of the ribosome act as a recognition signal, known as the signal sequence, or signal peptide.

The signal sequence binds to a complex of proteins known as a signal recognition particle, which temporarily inhibits further growth of the polypeptide chain on the ribosome. The signal recognition particle then binds to a specific membrane protein on the surface of the granular endoplasmic reticulum. This binding restarts the process of protein assembly, and the growing polypeptide chain is fed through a protein complex in the endoplasmic reticulum membrane into the lumen of the reticulum (Figure 5-10). Upon completion of protein assembly, proteins that are to be secreted end up in the lumen of the granular endoplas-mic reticulum. Proteins that are destined to function as integral membrane proteins remain embedded in the reticulum membrane.

Within the lumen of the endoplasmic reticulum, enzymes remove the signal sequence from most proteins, and so this portion is not present in the final protein. In addition, carbohydrate groups are linked to various side chains in the proteins; almost all proteins secreted from the cell are glycoproteins.

Following these modifications, portions of the reticulum membrane bud off, forming vesicles that contain the newly synthesized proteins. These vesicles migrate to the Golgi apparatus (Figure 5-10) and fuse with the Golgi membranes. Vesicle budding, movement through the cytosol, and fusion with the Golgi membranes require the interaction of a number of proteins that initiate the budding process, serve as molecular motors that transport vesicles along micro-tubules, and provide the docking signals to direct the vesicles to the appropriate membrane. These processes require chemical energy derived from the hydrolysis of ATP and GTP.

Within the Golgi apparatus, the protein undergoes still further modification. Some of the carbohydrates that were added in the granular endoplasmic reticu-lum are now removed and new groups added. These new carbohydrate groups function as labels that can be recognized when the protein encounters various binding sites during the remainder of its trip through the cell.

While in the Golgi apparatus, the many different proteins that have been funneled into this organelle become sorted out according to their final destination. This sorting involves the binding of regions of a particular protein to specific proteins in the Golgi membrane that are destined to form vesicles targeted to a particular destination.

Following modification and sorting, the proteins are packaged into vesicles that bud off the surface of the Golgi membrane. Some of the vesicles travel to the plasma membrane where they fuse with the membrane and release their contents to the extracellular fluid, a process known as exocytosis (Chapter 6). Other vesicles dock and fuse with lysosome membranes, delivering digestive enzymes to the interior of this organelle. The specific interactions governing the formation and distribution of these vesicles from the Golgi apparatus are similar in mechanism to those involved in vesicular shuttling between the endoplasmic reticulum and the Golgi apparatus. Specific proteins on the surface of a vesicle are recognized by specific docking proteins on the surface of the membranes with which the vesicle finally fuses.

In contrast to this entire story, if a protein does not have a signal sequence, synthesis continues on a free ribosome until the completed protein is released into the cytosol. These proteins are not secreted but are destined to function within the cell. Many remain in the cytosol where they function, for example, as enzymes in various metabolic pathways. Others are targeted to particular cell organelles; for example, ribosomal proteins are directed to the nucleus where they combine with rRNA before returning to the cytosol as part of the ribosomal subunits. The specific location of a protein is determined by binding sites on the protein that bind to specific sites at the protein's destination. For example, in the case of the ribosomal proteins, they bind to sites on the nuclear pores that control access to the nucleus.

Vander et al.: Human I I. Basic Cell Functions I 5. Genetic Information and I I © The McGraw-Hill

Physiology: The Protein Synthesis Companies, 2001 Mechanism of Body Function, Eighth Edition

PART ONE Basic Cell Functions

Cytoplasm mRNA from Gene A

mRNA from Gene B

Free ribosome |

i/VV

Signal sequence- j

polypeptide chain

Granular endoplasmic reticulum

/-Carbohydrate y group

Cleaved signal sequences

Vesicle

Golgi apparatus

Lysosome

Secretory vesicle

Protein B

Secretory vesicle

Protein B

Protein A

Plasma membrane

Extracellular fluid

FIGURE 5-10

Pathway of proteins destined to be secreted by cells or transferred to lysosomes. [Q] EQU

Protein A

Plasma membrane

Extracellular fluid

FIGURE 5-10

Pathway of proteins destined to be secreted by cells or transferred to lysosomes. [Q] EQU

Vander et al.: Human Physiology: The Mechanism of Body Function, Eighth Edition

Genetic Information and Protein Synthesis CHAPTER FIVE

Genetic Information and Protein Synthesis CHAPTER FIVE

As we described earlier, although some mitochon-drial proteins can be synthesized within the mitochondria from mitochondrial DNA genes, most mito-chondrial proteins are coded by nuclear genes and are synthesized in the cytosol on free ribosomes. To gain access to the mitochondrial matrix, these proteins bind to recognition sites on the mitochondrial membrane; their folded conformation is unfolded, and they are fed through a pore complex into the mitochondrial matrix, a process similar to inserting a bound ribosomal protein into the lumen of the endoplasmic reticulum. In the mitochondrial matrix, the protein refolds into its functional conformation. A similar process delivers proteins to the lumen of peroxisomes.

Essentials of Human Physiology

Essentials of Human Physiology

This ebook provides an introductory explanation of the workings of the human body, with an effort to draw connections between the body systems and explain their interdependencies. A framework for the book is homeostasis and how the body maintains balance within each system. This is intended as a first introduction to physiology for a college-level course.

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Responses

  • riccardo
    How are proteins synthesized in the ribosomes till exocytosis?
    7 years ago
  • MONIKA
    Why are most proteins destined for secretion from the cell are glycoproteins?
    7 years ago
  • catriona
    How protein is secreted steps?
    5 years ago

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