Secretory pathway
Encyclopedia
The secretory pathway is a series of steps a cell
uses to move protein
s out of the cell; a process known as secretion. The path of a protein destined for secretion has its origins in the rough endoplasmic reticulum
, a membrane-bound compartment
in the cell. The protein then proceeds through the many compartments of the Golgi apparatus
and finally ends up in a vesicle
that fuses with the plasma membrane, dumping the proteins outside of the cell. At each step along the way there are crucial factors that determine how and if the protein will proceed. Some of these factors include regulation of transportation, selection of particular proteins, the mechanics of proceeding to the next step, and modifications
that can occur to the protein along the way. All of these factors contribute to how a protein arrives outside of a cell after being synthesized.
in the Golgi apparatus
and are secreted via exocytosis
, all around the cell. Cells that secrete constitutively have Golgi apparatus scattered throughout the cytoplasm
. Fibroblast
s, osteoblast
s and chondrocyte
s are some of the many cells that perform constitutive secretion.
In regulated secretion, proteins are packaged as described in the constitutive pathway, but they are only secreted in response to a specific signal, such as neural
or hormonal
stimulation. Cells that use the regulated secretory pathway are usually apical or polarized, meaning that they secrete multiple classes of proteins. The Golgi apparatus
is found in a supranuclear position (between the nucleus and the secretory surface). Examples of cells that use regulated pathway are: goblet cells (secrete mucus
), beta cell
s of the pancreas (secrete insulin
) and odontoblast
s (secrete dentin
). The protein pathway consists of eight steps total.
journey out of the cell is getting into the endoplasmic reticulum
. Two methods exist for proteins to accomplish this. One is co-translational translocation and the other is post-translational translocation.
Cell (biology)
The cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of life that is classified as a living thing, and is often called the building block of life. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos....
uses to move protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
s out of the cell; a process known as secretion. The path of a protein destined for secretion has its origins in the rough endoplasmic reticulum
Endoplasmic reticulum
The endoplasmic reticulum is an organelle of cells in eukaryotic organisms that forms an interconnected network of tubules, vesicles, and cisternae...
, a membrane-bound compartment
Cellular compartment
Cellular compartments in cell biology comprise all closed parts within a cell, usually surrounded by a single or double lipid layer membrane. Most organelles are compartments like mitochondria, chloroplasts , peroxisomes, lysosomes, the endoplasmic reticulum, the cell nucleus or the Golgi apparatus...
in the cell. The protein then proceeds through the many compartments of the Golgi apparatus
Golgi apparatus
The Golgi apparatus is an organelle found in most eukaryotic cells. It was identified in 1898 by the Italian physician Camillo Golgi, after whom the Golgi apparatus is named....
and finally ends up in a vesicle
Vesicle (biology)
A vesicle is a bubble of liquid within another liquid, a supramolecular assembly made up of many different molecules. More technically, a vesicle is a small membrane-enclosed sack that can store or transport substances. Vesicles can form naturally because of the properties of lipid membranes , or...
that fuses with the plasma membrane, dumping the proteins outside of the cell. At each step along the way there are crucial factors that determine how and if the protein will proceed. Some of these factors include regulation of transportation, selection of particular proteins, the mechanics of proceeding to the next step, and modifications
Posttranslational modification
Posttranslational modification is the chemical modification of a protein after its translation. It is one of the later steps in protein biosynthesis, and thus gene expression, for many proteins....
that can occur to the protein along the way. All of these factors contribute to how a protein arrives outside of a cell after being synthesized.
General Regulation
In general, there are two different patterns of secretion. One pattern is called constitutive secretion. Proteins are continuously secreted from the cell regardless of environmental factors. No external signals are needed to initiate this process. Proteins are packaged in vesiclesVesicle (biology)
A vesicle is a bubble of liquid within another liquid, a supramolecular assembly made up of many different molecules. More technically, a vesicle is a small membrane-enclosed sack that can store or transport substances. Vesicles can form naturally because of the properties of lipid membranes , or...
in the Golgi apparatus
Golgi apparatus
The Golgi apparatus is an organelle found in most eukaryotic cells. It was identified in 1898 by the Italian physician Camillo Golgi, after whom the Golgi apparatus is named....
and are secreted via exocytosis
Exocytosis
Exocytosis , also known as 'The peni-cytosis', is the durable process by which a cell directs the contents of secretory vesicles out of the cell membrane...
, all around the cell. Cells that secrete constitutively have Golgi apparatus scattered throughout the cytoplasm
Cytoplasm
The cytoplasm is a small gel-like substance residing between the cell membrane holding all the cell's internal sub-structures , except for the nucleus. All the contents of the cells of prokaryote organisms are contained within the cytoplasm...
. Fibroblast
Fibroblast
A fibroblast is a type of cell that synthesizes the extracellular matrix and collagen, the structural framework for animal tissues, and plays a critical role in wound healing...
s, osteoblast
Osteoblast
Osteoblasts are mononucleate cells that are responsible for bone formation; in essence, osteoblasts are specialized fibroblasts that in addition to fibroblastic products, express bone sialoprotein and osteocalcin.Osteoblasts produce a matrix of osteoid, which is composed mainly of Type I collagen...
s and chondrocyte
Chondrocyte
Chondrocytes are the only cells found in cartilage. They produce and maintain the cartilaginous matrix, which consists mainly of collagen and proteoglycans...
s are some of the many cells that perform constitutive secretion.
In regulated secretion, proteins are packaged as described in the constitutive pathway, but they are only secreted in response to a specific signal, such as neural
Nerve
A peripheral nerve, or simply nerve, is an enclosed, cable-like bundle of peripheral axons . A nerve provides a common pathway for the electrochemical nerve impulses that are transmitted along each of the axons. Nerves are found only in the peripheral nervous system...
or hormonal
Hormone
A hormone is a chemical released by a cell or a gland in one part of the body that sends out messages that affect cells in other parts of the organism. Only a small amount of hormone is required to alter cell metabolism. In essence, it is a chemical messenger that transports a signal from one...
stimulation. Cells that use the regulated secretory pathway are usually apical or polarized, meaning that they secrete multiple classes of proteins. The Golgi apparatus
Golgi apparatus
The Golgi apparatus is an organelle found in most eukaryotic cells. It was identified in 1898 by the Italian physician Camillo Golgi, after whom the Golgi apparatus is named....
is found in a supranuclear position (between the nucleus and the secretory surface). Examples of cells that use regulated pathway are: goblet cells (secrete mucus
Mucus
In vertebrates, mucus is a slippery secretion produced by, and covering, mucous membranes. Mucous fluid is typically produced from mucous cells found in mucous glands. Mucous cells secrete products that are rich in glycoproteins and water. Mucous fluid may also originate from mixed glands, which...
), beta cell
Beta cell
Beta cells are a type of cell in the pancreas located in the so-called islets of Langerhans. They make up 65-80% of the cells in the islets.-Function:...
s of the pancreas (secrete insulin
Insulin
Insulin is a hormone central to regulating carbohydrate and fat metabolism in the body. Insulin causes cells in the liver, muscle, and fat tissue to take up glucose from the blood, storing it as glycogen in the liver and muscle....
) and odontoblast
Odontoblast
In vertebrates, an odontoblast is a biological cell of neural crest origin that is part of the outer surface of the dental pulp, and whose biological function is dentinogenesis, which is the creation of dentin, the substance under the tooth enamel....
s (secrete dentin
Dentin
Dentine is a calcified tissue of the body, and along with enamel, cementum, and pulp is one of the four major components of teeth. Usually, it is covered by enamel on the crown and cementum on the root and surrounds the entire pulp...
). The protein pathway consists of eight steps total.
Protein Translocation
The first step in a protein'sProtein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
journey out of the cell is getting into the endoplasmic reticulum
Endoplasmic reticulum
The endoplasmic reticulum is an organelle of cells in eukaryotic organisms that forms an interconnected network of tubules, vesicles, and cisternae...
. Two methods exist for proteins to accomplish this. One is co-translational translocation and the other is post-translational translocation.
- Co-Translational translocation is the action of a protein being fed into the ER as it is synthesized by the ribosomeRibosomeA ribosome is a component of cells that assembles the twenty specific amino acid molecules to form the particular protein molecule determined by the nucleotide sequence of an RNA molecule....
. In this scenario the protein begins to be translated normally. As the N-terminus (the first end of the protein to be synthesized) leaves the ribosome, a short sequence of the nascent protein's amino acidsAmino acidAmino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...
is recognized by a protein complex called SRPSignal recognition particleThe signal recognition particle is an abundant, cytosolic, universally conserved ribonucleoprotein that recognizes and targets specific proteins to the endoplasmic reticulum in eukaryotes and the plasma membrane in prokaryotes....
, or signal recognition particle. SRP binds to this sequence of amino acids and then subsequently binds to a protein complex called the SRP receptor embedded in the ER membrane. Both the SRP complex and SRP receptor complex hydrolyze a molecule of GTPGuanosine triphosphateGuanosine-5'-triphosphate is a purine nucleoside triphosphate. It can act as a substrate for the synthesis of RNA during the transcription process...
into GDPGuanosine diphosphateGuanosine diphosphate, abbreviated GDP, is a nucleoside diphosphate. It is an ester of pyrophosphoric acid with the nucleoside guanosine. GDP consists of the pyrophosphate group, the pentose sugar ribose, and the nucleobase guanine....
. Once this occurs the growing protein chain is moved to a membrane channel called the transloconTransloconThe translocon is the complex of proteins associated with the translocation of nascent polypeptides across membranes. In eukaryotes the polypeptides are transported into the interior space of the endoplasmic reticulum from the cytosol...
. It is through this hole in the ER membrane that the protein passes through as it is synthesized. The result of all this is a new protein residing within the membrane of the endoplasmic reticulum.
- Post-Translational translocation is the action of a protein passing into the ER following synthesis by the ribosomeRibosomeA ribosome is a component of cells that assembles the twenty specific amino acid molecules to form the particular protein molecule determined by the nucleotide sequence of an RNA molecule....
.
Sources
- Lodish, Harvey, et al. (2003) Molecular Cell Biology 5th Edition. W. H. Freeman