Photoactivated adenylyl cyclase (PAC) is a
protein consisting of an
adenylyl cyclaseenzyme 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, an important
second messenger in many cells. In the unicellular flagellate Euglena gracilis, PACα and PACβ (euPACs) serve as a photoreceptor complex that senses light for
photophobic responses and
phototaxis.[2] Small but potent PACs were identified in the genome of the bacteria Beggiatoa (bPAC) and Oscillatoria acuminata (OaPAC).[3][1] While natural bPAC has some enzymatic activity in the absence of light, variants with no dark activity have been engineered (PACmn).[4]
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, blue light illumination speeds up the swimming of transgenic sperm cells and aids
fertilization.[5] When expressed in
neurons, illumination changes the branching pattern of growing
axons.[6] PAC has been used in mice to clarify the function of neurons in the
hypothalamus, which use cAMP signaling to control mating behavior.[7] 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.[8][9]
Rhodopsin guanylyl cyclases
Photoactivated
guanylyl cyclases have been discovered in the aquatic fungi Blastocladiella emersonii[10][11] and Catenaria anguillulae.[12] Unlike PACs, these light-activated cyclases use
retinal as their light sensor and are therefore
rhodopsin guanylyl cyclases (RhGC). When expressed in
Xenopus oocytes or mammalian
neurons, RhGCs generate
cGMP in response to green light.[12] Therefore, they are considered useful
optogenetic tools to investigate
cGMP signaling.[13]