Photoactivated adenylyl cyclase (PAC) is a

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 ...

consisting of an

adenylyl cyclase Adenylate cyclase (EC 4.6.1.1, also commonly known as adenyl cyclase and adenylyl cyclase, abbreviated AC) is an enzyme with systematic name ATP diphosphate-lyase (cyclizing; 3′,5′-cyclic-AMP-forming). It catalyzes the following reaction: :A ...

enzyme domain directly linked to a BLUF (blue light receptor using FAD) type light sensor domain. When illuminated with blue light, the enzyme domain becomes active and converts ATP to

cAMP Camp may refer to: Outdoor accommodation and recreation * Campsite or campground, a recreational outdoor sleeping and eating site * a temporary settlement for nomads * Camp, a term used in New England, Northern Ontario and New Brunswick to descri ...

, an important

second messenger Second messengers are intracellular signaling molecules released by the cell in response to exposure to extracellular signaling molecules—the first messengers. (Intercellular signals, a non-local form or cell signaling, encompassing both first me ...

in many cells. In the unicellular flagellate '' Euglena gracilis,'' PACα and PACβ (euPACs) serve as a photoreceptor complex that senses light for

photophobic Photophobia is a medical symptom of abnormal intolerance to visual perception of light. As a medical symptom photophobia is not a morbid fear or phobia, but an experience of discomfort or pain to the eyes due to light exposure or by presence o ...

responses and

phototaxis Phototaxis is a kind of taxis, or locomotory movement, that occurs when a whole organism moves towards or away from a stimulus of light. This is advantageous for phototrophic organisms as they can orient themselves most efficiently to receive li ...

. Small but potent PACs were identified in the genome of the bacteria ''

Beggiatoa ''Beggiatoa'' is a genus of ''Gammaproteobacteria'' belonging the order ''Thiotrichales,'' in the ''Pseudomonadota'' phylum. This genus was one of the first bacteria discovered by Ukrainian botanist Sergei Sergei Winogradsky, Winogradsky. During ...

'' (bPAC) and ''

Oscillatoria ''Oscillatoria'' is a genus of filamentous cyanobacterium which is often found in freshwater environments, such as hot springs, and appears blue-green. Its name refers to the oscillating motion of its filaments as they slide against each other ...

acuminata'' (OaPAC). While natural bPAC has some enzymatic activity in the absence of light, variants with no dark activity have been engineered (PACmn).

Use of PACs as optogenetic tools

As PACs consist of a light sensor and an enzyme in a single protein, they can be expressed in other species and cell types to manipulate cAMP levels with light. When bPAC is expressed in mouse

sperm Sperm is the male reproductive cell, or gamete, in anisogamous forms of sexual reproduction (forms in which there is a larger, female reproductive cell and a smaller, male one). Animals produce motile sperm with a tail known as a flagellum, whi ...

, blue light illumination speeds up the swimming of transgenic sperm cells and aids

fertilization Fertilisation or fertilization (see spelling differences), also known as generative fertilisation, syngamy and impregnation, is the fusion of gametes to give rise to a new individual organism or offspring and initiate its development. Proce ...

. When expressed in

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. N ...

, illumination changes the branching pattern of growing

axons An axon (from Greek ἄξων ''áxōn'', axis), or nerve fiber (or nerve fibre: see American and British English spelling differences#-re, -er, spelling differences), is a long, slender projection of a nerve cell, or neuron, in vertebrates, th ...

. PAC has been used in mice to clarify the function of neurons in the

hypothalamus The hypothalamus () is a part of the brain that contains a number of small nuclei with a variety of functions. One of the most important functions is to link the nervous system to the endocrine system via the pituitary gland. The hypothalamu ...

, which use cAMP signaling to control mating behavior. Expression of PAC together with K⁺-specific cyclic-nucleotide-gated ion channels (CNGs) has been used to hyperpolarize neurons at very low light levels, which prevents them from firing action potentials.

Other light-activated cyclases

Photoactivated guanylyl cyclases have been discovered in the aquatic fungi ''

Blastocladiella ''Blastocladiella'' is a genus of fungus A fungus ( : fungi or funguses) is any member of the group of eukaryotic organisms that includes microorganisms such as yeasts and molds, as well as the more familiar mushrooms. These organisms a ...

emersonii'' and '' Catenaria anguillulae''. Unlike PACs, these light-activated cyclases use

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 retin ...

as their light sensor and are therefore

rhodopsin Rhodopsin, also known as visual purple, is a protein encoded by the RHO gene and a G-protein-coupled receptor (GPCR). It is the opsin of the rod cells in the retina and a light-sensitive receptor protein that triggers visual phototransduction ...

guanylyl cyclases (RhGC). When expressed in

Xenopus ''Xenopus'' () (Gk., ξενος, ''xenos''=strange, πους, ''pous''=foot, commonly known as the clawed frog) is a genus of highly aquatic frogs native to sub-Saharan Africa. Twenty species are currently described within it. The two best-known ...

oocytes or mammalian

, RhGCs generate cGMP in response to green light. Therefore, they are considered useful optogenetic tools to investigate cGMP signaling.

References

{{Reflist Protein families Enzymes by function Cell biology Neurochemistry