Halorhodopsin is a light-gated ion pump, specific for chloride ions, found in archaea, known as halobacteria. It is a seven-transmembrane

retinylidene protein Retinylidene proteins, are proteins that use retinal as a chromophore for light reception. They are the molecular basis for a variety of light-sensing systems from phototaxis in flagellates to eyesight in animals. Retinylidene proteins include a ...

from

microbial rhodopsin Microbial rhodopsins, also known as bacterial rhodopsins are retinal-binding proteins that provide light-dependent ion transport and sensory functions in halophilic and other bacteria. They are integral membrane proteins with seven transmembr ...

family. It is similar in tertiary structure (but not primary sequence structure) to vertebrate rhodopsins, the pigments that sense light in the

retina The retina (from la, rete "net") is the innermost, light-sensitive layer of tissue of the eye of most vertebrates and some molluscs. The optics of the eye create a focused two-dimensional image of the visual world on the retina, which then ...

. Halorhodopsin also shares sequence similarity to channelrhodopsin, another light-driven ion channel. Halorhodopsin contains the essential light-isomerizable

vitamin A Vitamin A is a fat-soluble vitamin and an essential nutrient for humans. It is a group of organic compounds that includes retinol, retinal (also known as retinaldehyde), retinoic acid, and several provitamin A carotenoids (most notably ...

derivative all-trans-

retinal Retinal (also known as retinaldehyde) is a polyene chromophore. Retinal, bound to proteins called opsins, is the chemical basis of visual phototransduction, the light-detection stage of visual perception (vision). Some microorganisms use re ...

. Due to the intense attention on solving the structure and function of this molecule, halorhodopsin is one of the few membrane proteins whose

crystal structure In crystallography, crystal structure is a description of the ordered arrangement of atoms, ions or molecules in a crystalline material. Ordered structures occur from the intrinsic nature of the constituent particles to form symmetric patterns t ...

is known. Halorhodopsin uses the energy of green/yellow light to move chloride ions into the cell, overcoming the membrane potential. Beside chlorides it transports other

halide In chemistry, a halide (rarely halogenide) is a binary chemical compound, of which one part is a halogen atom and the other part is an element or radical that is less electronegative (or more electropositive) than the halogen, to make a f ...

s and

nitrate Nitrate is a polyatomic ion with the chemical formula . Salts containing this ion are called nitrates. Nitrates are common components of fertilizers and explosives. Almost all inorganic nitrates are soluble in water. An example of an insoluble ...

s into the cell. Potassium chloride uptake by cells helps to maintain

osmotic balance Osmoregulation is the active regulation of the osmotic pressure of an organism's body fluids, detected by osmoreceptors, to maintain the homeostasis of the organism's water content; that is, it maintains the fluid balance and the concentration of ...

during cell growth. By performing the same task, light-driven anion pumps can considerably reduce the use of metabolic energy. Halorhodopsin has been the subject of much study and its structure is accurately known. Its properties are similar to those of bacteriorhodopsin, and these two light-driven ion pumps transport cations and anions in opposite directions. Halorhodopsin isoforms can be found in multiple species of halobacteria, including '' Halobacterium salinarum'', and ''

Natronobacterium pharaonis In taxonomy, ''Natronobacterium'' is a genus of the Natrialbaceae.See the NCBIbr>webpage on Natronobacterium Data extracted from the A member of the domain Archaea, it is both an extreme halophile and alkaliphile, thriving at an optimum saline ...

''. Much ongoing research is exploring these differences, and using them to parse apart the photocycle and pump properties. After bacteriorhodopsin, halorhodopsin may be the best type I (microbial) opsin studied. Peak absorbance of the halorhodopsin

complex is about 570 nm. Just as the blue-light activated ion channel channelrhodopsin-2 opens up the ability to activate excitable cells (such as

neuron A neuron, neurone, or nerve cell is an membrane potential#Cell excitability, electrically excitable cell (biology), cell that communicates with other cells via specialized connections called synapses. The neuron is the main component of nervous ...

muscle cell A muscle cell is also known as a myocyte when referring to either a cardiac muscle cell (cardiomyocyte), or a smooth muscle cell as these are both small cells. A skeletal muscle cell is long and threadlike with many nuclei and is called a m ...

s, pancreatic cells, and immune cells) with brief pulses of blue light, halorhodopsin opens up the ability to silence excitable cells with brief pulses of yellow light. Thus halorhodopsin and channelrhodopsin together enable multiple-color optical activation, silencing, and desynchronization of neural activity, creating a powerful neuroengineering toolbox. Halorhodopsin from '' Natronomonas'' (NpHR) has been used to achieve inhibition of

action potential An action potential occurs when the membrane potential of a specific cell location rapidly rises and falls. This depolarization then causes adjacent locations to similarly depolarize. Action potentials occur in several types of animal cells, ...

s in neurons in mammalian systems. Since light activation of NpHR leads to an influx of chloride ions which is a part of the natural process for generating hyperpolarization, NpHR induced inhibition works very well in neurons. Original NpHR channels when expressed in mammalian cells, showed a tendency to get accumulated in the

endoplasmic reticulum The endoplasmic reticulum (ER) is, in essence, the transportation system of the eukaryotic cell, and has many other important functions such as protein folding. It is a type of organelle made up of two subunits – rough endoplasmic reticulum ( ...

of the cells. To overcome the sub-cellular localization issues, an ER export motif was added to the NpHR sequence. This modified NpHR (called eNpHR2.0) was utilized successfully to drive aggregate-free, high level expression of NpHR in vivo. However, even the modified form of NpHR showed poor localization at the

cell membrane The cell membrane (also known as the plasma membrane (PM) or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of all cells from the outside environment (the ...

. To achieve higher membrane-localization it was further modified by addition of a golgi export signal and membrane trafficking signal from a potassium channel (Kir2.1). The addition of Kir2.1 signal significantly improved the membrane localization of NpHR and this engineered form of NpHR was labeled eNpHR3.0

As a research tool

Halorhodopsin is used in

optogenetics Optogenetics is a biological technique to control the activity of neurons or other cell types with light. This is achieved by expression of light-sensitive ion channels, pumps or enzymes specifically in the target cells. On the level of indiv ...

to hyperpolarize (or inhibit) specific

neurons A neuron, neurone, or nerve cell is an electrically excitable cell that communicates with other cells via specialized connections called synapses. The neuron is the main component of nervous tissue in all animals except sponges and placozoa. ...

References

External links

Synthetic Neurobiology Group, MIT: Halorhodopsin mediating optical silencing of neurons
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Optogenetics Resource Center

OpenOptogenetics.org, an open wiki about optogenetics
{{Ion pumps 7TM receptors Integral membrane proteins