A membrane transport protein (or simply transporter) is a

membrane protein Membrane proteins are common proteins that are part of, or interact with, biological membranes. Membrane proteins fall into several broad categories depending on their location. Integral membrane proteins are a permanent part of a cell membrane ...

involved in the movement of

ion An ion () is an atom or molecule with a net electrical charge. The charge of an electron is considered to be negative by convention and this charge is equal and opposite to the charge of a proton, which is considered to be positive by conve ...

s, small

molecule A molecule is a group of two or more atoms held together by attractive forces known as chemical bonds; depending on context, the term may or may not include ions which satisfy this criterion. In quantum physics, organic chemistry, and bioch ...

s, and macromolecules, such as another

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...

, across a biological membrane. Transport proteins are

integral In mathematics Mathematics is an area of knowledge that includes the topics of numbers, formulas and related structures, shapes and the spaces in which they are contained, and quantities and their changes. These topics are represented i ...

transmembrane protein A transmembrane protein (TP) is a type of integral membrane protein that spans the entirety of the cell membrane. Many transmembrane proteins function as gateways to permit the transport of specific substances across the membrane. They frequent ...

s; that is they exist permanently within and span the membrane across which they transport substances. The proteins may assist in the movement of substances by

facilitated diffusion Facilitated diffusion (also known as facilitated transport or passive-mediated transport) is the process of spontaneous passive transport (as opposed to active transport) of molecules or ions across a biological membrane via specific transmembra ...

active transport In cellular biology, ''active transport'' is the movement of molecules or ions across a cell membrane from a region of lower concentration to a region of higher concentration—against the concentration gradient. Active transport requires cellul ...

. The two main types of proteins involved in such transport are broadly categorized as either ''channels'' or ''carriers''. The solute carriers and

atypical SLCs Atypical Solute Carrier Families (Atypical SLCs) are novel plausible secondary active or facilitative transporter proteins that share ancestral background with the known solute carrier families (SLCs). However, they have not been assigned a name a ...

are secondary active or facilitative transporters in humans. Collectively membrane transporters and channels are known as the transportome. Transportomes govern cellular influx and efflux of not only ions and nutrients but drugs as well.

Difference between channels and carriers

A carrier is not open simultaneously to both the extracellular and intracellular environments. Either its inner gate is open, or outer gate is open. In contrast, a channel can be open to both environments at the same time, allowing the molecules to diffuse without interruption. Carriers have binding sites, but pores and channels do not. When a channel is opened, millions of ions can pass through the membrane per second, but only 100 to 1000 molecules typically pass through a carrier molecule in the same time. Each carrier protein is designed to recognize only one substance or one group of very similar substances. Research has correlated defects in specific carrier proteins with specific diseases.

Active transport

Active transport In cellular biology, ''active transport'' is the movement of molecules or ions across a cell membrane from a region of lower concentration to a region of higher concentration—against the concentration gradient. Active transport requires cellul ...

is the movement of a substance across a membrane against its concentration gradient. This is usually to accumulate high concentrations of molecules that a cell needs, such as glucose or amino acids. If the process uses chemical energy, such as adenosine triphosphate (ATP), it is called primary active transport.

Secondary active transport In cellular biology, ''active transport'' is the movement of molecules or ions across a cell membrane from a region of lower concentration to a region of higher concentration—against the concentration gradient. Active transport requires cellul ...

involves the use of an

electrochemical gradient An electrochemical gradient is a gradient of electrochemical potential, usually for an ion that can move across a membrane. The gradient consists of two parts, the chemical gradient, or difference in solute concentration across a membrane, and ...

, and does not use energy produced in the cell.Ashley, Ruth. Hann, Gary. Han, Seong S. Cell Biology. New Age International Publishers. . p. 113. Unlike channel proteins which only transport substances through membranes passively, carrier proteins can transport ions and molecules either passively through facilitated diffusion, or via secondary active transport. A carrier protein is required to move particles from areas of low concentration to areas of high concentration. These carrier proteins have receptors that bind to a specific molecule (substrate) needing transport. The molecule or ion to be transported (the substrate) must first bind at a binding site at the carrier molecule, with a certain binding affinity. Following binding, and while the binding site is facing the same way, the carrier will capture or occlude (take in and retain) the substrate within its molecular structure and cause an internal translocation so that the opening in the protein now faces the other side of the plasma membrane. The carrier protein substrate is released at that site, according to its binding affinity there.

Facilitated diffusion

Facilitated diffusion Facilitated diffusion (also known as facilitated transport or passive-mediated transport) is the process of spontaneous passive transport (as opposed to active transport) of molecules or ions across a biological membrane via specific transmembra ...

is the passage of molecules or ions across a biological membrane through specific transport proteins and requires no energy input. Facilitated diffusion is used especially in the case of large polar molecules and charged ions; once such ions are dissolved in water they cannot diffuse freely across cell membranes due to the hydrophobic nature of the fatty acid tails of the phospholipids that make up the bilayers. The type of carrier proteins used in facilitated diffusion is slightly different from those used in active transport. They are still transmembrane carrier proteins, but these are gated transmembrane channels, meaning they do not internally translocate, nor require ATP to function. The substrate is taken in one side of the gated carrier, and without using ATP the substrate is released into the cell.

Reverse diffusion

Reverse transport Reverse transport, or transporter reversal, is a phenomenon in which the substrates of a membrane transport protein are moved in the opposite direction to that of their typical movement by the transporter. Transporter reversal typically occurs when ...

, or ''transporter reversal'', is a phenomenon in which the substrates of a membrane transport protein are moved in the opposite direction to that of their typical movement by the transporter. Transporter reversal typically occurs when a membrane transport protein is

phosphorylated In chemistry, phosphorylation is the attachment of a phosphate group to a molecule or an ion. This process and its inverse, dephosphorylation, are common in biology and could be driven by natural selection. Text was copied from this source, wh ...

by a particular

protein kinase A protein kinase is a kinase which selectively modifies other proteins by covalently adding phosphates to them (phosphorylation) as opposed to kinases which modify lipids, carbohydrates, or other molecules. Phosphorylation usually results in a fu ...

, which is an

enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. A ...

that adds a

phosphate In chemistry, a phosphate is an anion, salt, functional group or ester derived from a phosphoric acid. It most commonly means orthophosphate, a derivative of orthophosphoric acid . The phosphate or orthophosphate ion is derived from phospho ...

group to proteins.

Types

(Grouped by Transporter Classification database categories)

1: Channels/pores

* α-helical protein channels such as voltage-gated ion channel (VIC),

ligand-gated ion channels Ligand-gated ion channels (LICs, LGIC), also commonly referred to as ionotropic receptors, are a group of transmembrane ion-channel proteins which open to allow ions such as Na+, K+, Ca2+, and/or Cl− to pass through the membrane in res ...

(LGICs) * β-barrel porins such as

aquaporin Aquaporins, also called water channels, are channel proteins from a larger family of major intrinsic proteins that form pores in the membrane of biological cells, mainly facilitating transport of water between cells. The cell membranes of a ...

* channel-forming toxins, including

colicins A colicin is a type of bacteriocin produced by and toxic to some strains of ''Escherichia coli''. Colicins are released into the environment to reduce competition from other bacterial strains. Colicins bind to outer membrane receptors, using them ...

diphtheria toxin Diphtheria toxin is an exotoxin secreted by '' Corynebacterium diphtheriae'', the pathogenic bacterium that causes diphtheria. The toxin gene is encoded by a prophageA prophage is a virus that has inserted itself into the genome of the host ...

, and others * Nonribosomally synthesized channels such as

gramicidin Gramicidin, also called gramicidin D, is a mix of ionophoric antibiotics, gramicidin A, B and C, which make up about 80%, 5%, and 15% of the mix, respectively. Each has 2 isoforms, so the mix has 6 different types of gramicidin molecules. They c ...

* Holins; which function in export of enzymes that digest bacterial cell walls in an early step of cell lysis. Facilitated diffusion occurs in and out of the cell membrane via channels/pores and carriers/porters. Note: * Channels: Channels are either in open state or closed state. When a channel is opened with a slight conformational switch, it is open to both environment simultaneously (extracellular and intracellular) * Symport

Pores: Pores are continuously open to these both environment, because they do not undergo conformational changes. They are always open and active.

2: Electrochemical potential-driven transporters

Also named carrier proteins or secondary carriers. * 2.A: Porters (

uniporters Facilitated diffusion (also known as facilitated transport or passive-mediated transport) is the process of spontaneous passive transport (as opposed to active transport) of molecules or ions across a biological membrane via specific transmem ...

, symporters,

antiporters An antiporter (also called exchanger or counter-transporter) is a cotransporter and integral membrane protein involved in secondary active transport of two or more different molecules or ions across a phospholipid membrane such as the plasma mem ...

), SLCs. **

Excitatory amino acid transporter Glutamate transporters are a family of neurotransmitter transporter proteins that move glutamate – the principal excitatory neurotransmitter – across a membrane. The family of glutamate transporters is composed of two primary subclasses: the ex ...

s (EAATs) ***

EAAT1 Excitatory amino acid transporter 1 (EAAT1) is a protein that, in humans, is encoded by the ''SLC1A3'' gene. EAAT1 is also often called the GLutamate ASpartate Transporter 1 (GLAST-1). EAAT1 is predominantly expressed in the plasma membrane, al ...

***

EAAT2 Excitatory amino acid transporter 2 (EAAT2) also known as solute carrier family 1 member 2 (SLC1A2) and glutamate transporter 1 (GLT-1) is a protein that in humans is encoded by the ''SLC1A2'' gene. Alternatively spliced transcript variants of thi ...

***

EAAT3 Excitatory amino acid transporter 3 (EAAT3), is a protein that in humans is encoded by the ''SLC1A1'' gene. Tissue distribution EAAT3 is expressed on the plasma membrane of neurons, specifically on the dendrites and axon terminals. Function E ...

***

EAAT4 Excitatory amino-acid transporter 4 (EAAT4) is a protein that in humans is encoded by the ''SLC1A6'' gene. EAAT4 is expressed predominantly in the cerebellum, has high affinity for the excitatory amino acids L-aspartate and L-glutamate Glut ...

***

EAAT5 Excitatory amino-acid transporter 5 (EAAT5) is a protein that in humans is encoded by the ''SLC1A7'' gene. EAAT5 is expressed predominantly in the retina, has high affinity for the excitatory amino acid L-glutamate Glutamic acid (symbol Glu ...

Glucose transporter Glucose transporters are a wide group of membrane proteins that facilitate the transport of glucose across the plasma membrane, a process known as facilitated diffusion. Because glucose is a vital source of energy for all life, these transporter ...

Monoamine transporter Monoamine transporters (MATs) are protein structures that function as integral plasma-membrane transporters to regulate concentrations of extracellular monoamine neurotransmitters. Three major classes of MATs (SERT, DAT, NET) are responsible fo ...

s, including: ***

Dopamine transporter The dopamine transporter (also dopamine active transporter, DAT, SLC6A3) is a membrane-spanning protein that pumps the neurotransmitter dopamine out of the synaptic cleft back into cytosol. In the cytosol, other transporters sequester the dop ...

(DAT) ***

Norepinephrine transporter The norepinephrine transporter (NET), also known as noradrenaline transporter (NAT), is a protein that in humans is encoded by the solute carrier family 6 member 2 (SLC6A2) gene. NET is a monoamine transporter and is responsible for the sodium- ...

(NET) ***

Serotonin transporter The serotonin transporter (SERT or 5-HTT) also known as the sodium-dependent serotonin transporter and solute carrier family 6 member 4 is a protein that in humans is encoded by the SLC6A4 gene. SERT is a type of monoamine transporter protein tha ...

(SERT) ***

Vesicular monoamine transporter The vesicular monoamine transporter (VMAT) is a transport protein integrated into the membranes of synaptic vesicles of presynaptic neurons. It transports monoamine neurotransmitters – such as dopamine, serotonin, norepinephrine, epinephri ...

s (VMAT) **

Adenine nucleotide translocator Adenine nucleotide translocator (ANT), also known as the ADP/ATP translocase (ANT), ADP/ATP carrier protein (AAC) or mitochondrial ADP/ATP carrier, exchanges free ATP with free ADP across the inner mitochondrial membrane. ANT is the most abund ...

(ANT) * 2.B: Nonribosomally synthesized porters, such as: ** The

Nigericin Nigericin is an antibiotic derived from '' Streptomyces hygroscopicus''. Its isolation was described in the 1950s, and in 1968 the structure could be elucidated by X-ray crystallography. The structure and properties of nigericin are similar to th ...

family ** The

Ionomycin Ionomycin is an ionophore and an antibiotic that binds calcium ions (Ca2+) in a ratio 1:1. It is produced by the bacterium '' Streptomyces conglobatus''. It binds also other divalent cations like magnesium and cadmium, but binds Ca2+ preferably. I ...

family * 2.C: Ion-gradient-driven energizers

3: Membrane transport protein

* 3.A: P-P-bond-hydrolysis-driven transporters : **

ATP-binding cassette transporter The ATP synthase, ATP-binding cassette transporters (ABC transporters) are a transport system superfamily that is one of the largest and possibly one of the oldest gene family, gene families. It is represented in all extant taxon, extant Phylum ...

(ABC transporter), such as MDR,

CFTR Cystic fibrosis transmembrane conductance regulator (CFTR) is a membrane protein and anion channel in vertebrates that is encoded by the ''CFTR'' gene. Geneticist Lap-Chee Tsui and his team identified the CFTR gene in 1989 as the gene linked wi ...

** V-type ATPase ; ( "V" related to vacuolar ). **

P-type ATPase The P-type ATPases, also known as E1-E2 ATPases, are a large group of evolutionarily related ion and lipid pumps that are found in bacteria, archaea, and eukaryotes. P-type ATPases are α-helical bundle primary transporters named based upon thei ...

; ( "P" related to phosphorylation), such as : *** Na⁺/K⁺-ATPase *** Plasma membrane Ca²⁺ ATPase ***

Proton pump A proton pump is an integral membrane protein pump that builds up a proton gradient across a biological membrane A biological membrane, biomembrane or cell membrane is a selectively permeable membrane that separates the interior of a cell f ...

F-type ATPase F-ATPase, also known as F-Type ATPase, is an ATPase/ synthase found in bacterial plasma membranes, in mitochondrial inner membranes (in oxidative phosphorylation, where it is known as Complex V), and in chloroplast thylakoid membranes. It u ...

; ("F" related to factor), including: mitochondrial ATP synthase, chloroplast ATP synthase1 * 3.B: Decarboxylation-driven transporters * 3.C: Methyltransfer-driven transporters * 3.D: Oxidoreduction-driven transporters * 3.E: Light absorption-driven transporters, such as rhodopsin

4: Group translocators

The group translocators provide a special mechanism for the phosphorylation of sugars as they are transported into bacteria (PEP group translocation)

5: Electron carriers

The transmembrane electron transfer carriers in the membrane include two-electron carriers, such as the disulfide bond oxidoreductases (DsbB and DsbD in E. coli) as well as one-electron carriers such as NADPH oxidase. Often these redox proteins are not considered transport proteins.

Examples

Every carrier protein, especially within the same cell membrane, is specific to one type or family of molecules. For example,

GLUT1 Glucose transporter 1 (or GLUT1), also known as solute carrier family 2, facilitated glucose transporter member 1 (SLC2A1), is a uniporter protein that in humans is encoded by the ''SLC2A1'' gene. GLUT1 facilitates the transport of glucose across ...

is a named carrier protein found in almost all animal cell membranes that transports glucose across the bilayer. Other specific carrier proteins also help the body function in important ways. Cytochromes operate in the electron transport chain as carrier proteins for electrons.

Pathology

A number of inherited diseases involve defects in carrier proteins in a particular substance or group of cells. Cysteinuria (cysteine in the urine and the bladder) is such a disease involving defective cysteine carrier proteins in the kidney cell membranes. This transport system normally removes cysteine from the fluid destined to become urine and returns this essential amino acid to the blood. When this carrier malfunctions, large quantities of cysteine remain in the urine, where it is relatively insoluble and tends to precipitate. This is one cause of urinary stones. Some vitamin carrier proteins have been shown to be overexpressed in patients with malignant disease. For example, levels of riboflavin carrier protein (RCP) have been shown to be significantly elevated in people with

breast cancer Breast cancer is cancer that develops from breast tissue. Signs of breast cancer may include a lump in the breast, a change in breast shape, dimpling of the skin, milk rejection, fluid coming from the nipple, a newly inverted nipple, or a re ...

.Rao, PN, Levine, E et al. Elevation of Serum Riboflavin Carrier Protein in Breast Cancer. Cancer Epidemiol Biomarkers Prev. Volume 8 No 11. pp. 985–990

References

Anderle, P., Barbacioru,C., Bussey, K., Dai, Z., Huang, Y., Papp, A., Reinhold, W., Sadee, W., Shankavaram, U., & Weinstein, J. (2004). Membrane Transporters and Channels: Role of the Transportome in Cancer Chemosensitivity and Chemoresistance. Cancer Research, 54, 4294-4301.

External links

* {{Ion pumps * Transmembrane transporters