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48-397: The afferent nerve fibers of the olfactory receptor neurons transmit nerve impulses about odors to the central nervous system ( olfaction ). Derived from the embryonic nasal placode , the olfactory nerve is somewhat unusual among cranial nerves because it is capable of some regeneration if damaged. The olfactory nerve is sensory in nature and originates on the olfactory mucosa in

96-436: A conformational change. This conformational change causes the alpha subunit to dissociate from the complex and become bound to GTP. This G-alpha-GTP complex then binds to adenylyl cyclase and causes activation and the release of cAMP. Since a good signal requires the help of enzymes, which turn on and off signals quickly, there must also be a mechanism in which adenylyl cyclase deactivates and inhibits cAMP. The deactivation of

144-570: A critical role in sperm motility. Adenylyl cyclase has been implicated in memory formation, functioning as a coincidence detector . AC-IV was first reported in the bacterium Aeromonas hydrophila , and the structure of the AC-IV from Yersinia pestis has been reported. These are the smallest of the AC enzyme classes; the AC-IV (CyaB) from Yersinia is a dimer of 19 kDa subunits with no known regulatory components ( PDB : 2FJT ​). AC-IV forms

192-460: A functional homodimer that resembles the mammalian architecture with two active sites. In non-animal class III ACs, the catalytic cytoplasmic domain is seen associated with other (not necessarily transmembrane) domains. Class III adenylyl cyclase domains can be further divided into four subfamilies, termed class IIIa through IIId. Animal membrane-bound ACs belong to class IIIa. The reaction happens with two metal cofactors (Mg or Mn) coordinated to

240-472: A key role in pathogenesis. Most AC-III's are integral membrane proteins involved in transducing extracellular signals into intracellular responses. A Nobel Prize was awarded to Earl Sutherland in 1971 for discovering the key role of AC-III in human liver, where adrenaline indirectly stimulates AC to mobilize stored energy in the "fight or flight" response. The effect of adrenaline is via a G protein signaling cascade, which transmits chemical signals from outside

288-406: A molecular and spatial manner due to receptor specificity. Some ORNs contain receptor proteins with high affinity for some odorants, with distinct odor selectivity to a specific chemical structure, while other receptor proteins are less selective. Damage to this nerve leads to impairment or total loss of the sense of smell ( anosmia ). To simply test the function of the olfactory nerve, each nostril

336-586: A second cytoplasmic domain called C2. The important parts for function are the N-terminus and the C1 and C2 regions. The C1a and C2a subdomains are homologous and form an intramolecular 'dimer' that forms the active site. In Mycobacterium tuberculosis and many other bacterial cases, the AC-III polypeptide is only half as long, comprising one 6-transmembrane domain followed by a cytoplasmic domain, but two of these form

384-422: A sensation in the brain only after information about the stimulus travels there via afferent nerve pathways. Afferent is derived from Latin participle afferentem ( af - = ad -  : to + ferre  : bear, carry), meaning carrying into , whereas efferent is derived from ex ferens , meaning carrying away (e- = ex- means 'from'). Ad and ex give an mnemonic device for remembering

432-443: A so-called second messenger . Adenylyl cyclases are often activated or inhibited by G proteins , which are coupled to membrane receptors and thus can respond to hormonal or other stimuli. Following activation of adenylyl cyclase, the resulting cAMP acts as a second messenger by interacting with and regulating other proteins such as protein kinase A and cyclic nucleotide-gated ion channels . Photoactivated adenylyl cyclase (PAC)

480-467: A superfamily with mammalian thiamine-triphosphatase called CYTH (CyaB, thiamine triphosphatase). These forms of AC have been reported in specific bacteria ( Prevotella ruminicola O68902 and Rhizobium etli Q8KY20 , respectively) and have not been extensively characterized. There are a few extra members (~400 in Pfam) known to be in class VI. Class VI enzymes possess a catalytic core similar to

528-423: A swelling in the dorsal root known as the dorsal root ganglion . All of the axons in the dorsal root, which contains afferent nerve fibers, are used in the transduction of somatosensory information. Somatosensory receptors include senses such as pain, touch, temperature, itch, and stretch. For example, a specific muscle fiber called an intrafusal muscle fiber is a type of afferent neuron that lies parallel to

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576-518: Is available for class I AC. Some indirect structural information is available for this class. It is known that the N-terminal half is the catalytic portion, and that it requires two Mg ions. S103, S113, D114, D116 and W118 are the five absolutely essential residues. The class I catalytic domain ( Pfam PF12633 ) belongs to the same superfamily ( Pfam CL0260 ) as the palm domain of DNA polymerase beta ( Pfam PF18765 ). Aligning its sequence onto

624-403: Is bound to an odor receptor protein, the alpha subunit of an olfactory-specific heterotrimeric G-protein, G olf , dissociates and activates olfactory-specific adenylate cyclase , adenylyl cyclase III (ACIII). Activation of ACIII leads to an increase in cyclic AMP (cAMP), which depolarizes the neuron due to an influx of Na+ and Ca2+ by opening cyclic nucleotide-gated ion channels . The neuron

672-726: Is further depolarized by a Ca2+-activated Cl- current travelling from the cilia, where the depolarization first occurred, to the axon hillock of the ORN. At the axon hillock, voltage-gated Na+ channels open and generate an action potential that is transmitted to the olfactory bulb . After transmission, the ORN membrane is repolarized by calcium/calmodulin kinase II-mediated mechanisms that work to extrude Ca2+ and transport Na+ via an Na+/Ca2+ exchanger, diminish cAMP levels by activating phosphodiesterases , and restore heterotrimeric G olf. ORN axons are responsible for relaying odorant information to CNS through action potentials. The ORN axons leave

720-414: Is regulated by G proteins, which can be found in the monomeric form or the heterotrimeric form, consisting of three subunits. Adenylyl cyclase activity is controlled by heterotrimeric G proteins. The inactive or inhibitory form exists when the complex consists of alpha, beta, and gamma subunits, with GDP bound to the alpha subunit. In order to become active, a ligand must bind to the receptor and cause

768-482: Is supported by the fact that adenylyl cyclases are coincidence detectors , meaning that they are activated only by several different signals occurring together. In peripheral cells and tissues adenylyl cyclases appear to form molecular complexes with specific receptors and other signaling proteins in an isoform-specific manner. Individual transmembrane adenylyl cyclase isoforms have been linked to numerous physiological functions. Soluble adenylyl cyclase (sAC, AC10) has

816-481: Is tested with a pungent odor. If the odor is smelled, the olfactory nerve is likely functioning. On the other hand, the nerve is only one of several reasons that could explain if the odor is not smelled. There are olfactory testing packets in which strong odors are embedded into cards and the responses of the patient to each odor can be determined. Lesions to the olfactory nerve can occur because of "blunt trauma", such as coup-contrecoup damage, meningitis, and tumors of

864-449: Is the most polyphyletic known enzyme : six distinct classes have been described, all catalyzing the same reaction but representing unrelated gene families with no known sequence or structural homology . The best known class of adenylyl cyclases is class III or AC-III (Roman numerals are used for classes). AC-III occurs widely in eukaryotes and has important roles in many human tissues . All classes of adenylyl cyclase catalyse

912-430: The brainstem . The second order neuron's projection decussates at the medulla through medial lemniscus to the third order neurons in the thalamus . The third order neuron's axon terminates at the primary somatosensory cortex of the parietal lobe . Types of afferent fibers include the general somatic , the general visceral , the special somatic and the special visceral afferent fibers . Alternatively, in

960-422: The central nervous system . Many afferent projections arrive at a particular brain region. In the peripheral nervous system , afferent nerve fibers are part of the sensory nervous system and arise from outside of the central nervous system. Sensory and mixed nerves contain afferent fibers. Afferent neurons are pseudounipolar neurons that have a single process leaving the cell body dividing into two branches:

1008-439: The extrafusal muscle fibers thus functions as a stretch receptor by detecting muscle length. All of these sensations travel along the same general pathways towards the brain. One pathway— dorsal column–medial lemniscus pathway —begins with sensation from the periphery being sent via afferent nerve fiber of the dorsal root ganglion (first order neuron) through the spinal cord to the dorsal column nuclei (second order neuron) in

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1056-408: The frontal lobe of the brain. These injuries often lead to a reduced ability to taste and smell. Lesions of the olfactory nerve do not lead to a reduced ability to sense pain from the nasal epithelium. This is because pain from the nasal epithelium is not carried to the central nervous system by the olfactory nerve - it is carried to the central nervous system by the trigeminal nerve . A decrease in

1104-486: The olfactory receptor neurons (ORNs) at the periphery and transmit olfactory information to the central nervous system via axons at the basal surface. These axons aggregate, forming the olfactory nerve. Therefore, the olfactory nerve works to transduce sensory stimuli in the form of odorants and encode them into electrical signals, which are relayed to higher-order centers through synaptic transmission . Odorants bind to specific odorant receptor proteins contained to

1152-404: The sensory system , afferent fibers can be classified by sizes with category specifications depending on if they innervate the skins or muscles. In the nervous system , there is a "closed loop" system of sensation, decision, and reactions. This process is carried out through the activity of sensory neurons, interneurons , and motor neurons . A touch or painful stimulus, for example, creates

1200-514: The AC-II to enter host cells, where the exogenous AC activity undermines normal cellular processes. The genes for Class II ACs are known as cyaA , one of which is anthrax toxin . Several crystal structures are known for AC-II enzymes. These adenylyl cyclases are the most familiar based on extensive study due to their important roles in human health. They are also found in some bacteria, notably Mycobacterium tuberculosis where they appear to have

1248-568: The Class II enzyme]). This was the first class of AC to be characterized. It was observed that E. coli deprived of glucose produce cAMP that serves as an internal signal to activate expression of genes for importing and metabolizing other sugars. cAMP exerts this effect by binding the transcription factor CRP , also known as CAP. Class I AC's are large cytosolic enzymes (~100 kDa) with a large regulatory domain (~50 kDa) that indirectly senses glucose levels. As of 2012 , no crystal structure

1296-532: The ability to smell is a normal consequence of human aging , and usually is more pronounced in men than in women. It is often unrecognized in patients except that they may note a decreased ability to taste (much of taste is actually based on reception of food odor). Some of this decrease results from repeated damage to the olfactory nerve receptors due likely to repeated upper respiratory infections. Patients with Alzheimer's disease almost always have an abnormal sense of smell when tested. Some nanoparticles entering

1344-474: The active G-alpha-GTP complex is accomplished rapidly by GTP hydrolysis due to the reaction being catalyzed by the intrinsic enzymatic activity of GTPase located in the alpha subunit. It is also regulated by forskolin , as well as other isoform-specific effectors: In neurons , calcium-sensitive adenylyl cyclases are located next to calcium ion channels for faster reaction to Ca influx; they are suspected of playing an important role in learning processes. This

1392-430: The adenylyl cyclase activity. There are ten known isoforms of adenylyl cyclases in mammals : These are also sometimes called simply AC1, AC2, etc., and, somewhat confusingly, sometimes Roman numerals are used for these isoforms that all belong to the overall AC class III. They differ mainly in how they are regulated, and are differentially expressed in various tissues throughout mammalian development. Adenylyl cyclase

1440-422: The behavior of the organism. A green-light activated rhodopsin adenylyl cyclase (CaRhAC) has recently been engineered by modifying the nucleotide binding pocket of rhodopsin guanylyl cyclase . Most class III adenylyl cyclases are transmembrane proteins with 12 transmembrane segments. The protein is organized with 6 transmembrane segments, then the C1 cytoplasmic domain, then another 6 membrane segments, and then

1488-452: The cell across the membrane to the inside of the cell ( cytoplasm ). The outside signal (in this case, adrenaline) binds to a receptor, which transmits a signal to the G protein, which transmits a signal to adenylyl cyclase, which transmits a signal by converting adenosine triphosphate to cyclic adenosine monophosphate (cAMP). cAMP is known as a second messenger . Cyclic AMP is an important molecule in eukaryotic signal transduction ,

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1536-513: The conversion of adenosine triphosphate (ATP) to 3',5'-cyclic AMP (cAMP) and pyrophosphate . Magnesium ions are generally required and appear to be closely involved in the enzymatic mechanism. The cAMP produced by AC then serves as a regulatory signal via specific cAMP-binding proteins , either transcription factors , enzymes (e.g., cAMP-dependent kinases ), or ion transporters . The first class of adenylyl cyclases occur in many bacteria including E. coli (as CyaA P00936 [unrelated to

1584-409: The long one towards the sensory organ , and the short one toward the central nervous system (e.g. spinal cord). These cells do have sensory afferent dendrites , similar to those typically inherent in neurons . They have a smooth and rounded cell body located in the ganglia of the peripheral nervous system. Just outside the spinal cord , thousands of afferent neuronal cell bodies are aggregated in

1632-465: The lungs or gut. Olfactory cilia are actin -rich protrusions supported by scaffolding proteins which help to localize odorant receptors and provide an increased cellular surface for odorant binding. Homologous to G-protein-coupled receptors (GPCRs) , olfactory receptor molecules consist of seven trans-membrane, hydrophobic domains and a cytoplasmic domain with a carboxyl terminal region that interacts with G-proteins and odorants. Once an odorant

1680-441: The many openings of the cribriform plate , a sieve -like structure of the ethmoid bone . The sense of smell arises from the stimulation of receptors by small molecules in inspired air of varying spatial, chemical, and electrical properties that reach the nasal epithelium in the nasal cavity during inhalation. These stimulants are transduced into electrical activity in the olfactory neurons, which then transmit these impulses to

1728-514: The nasal passages, inhaled odorant molecules interact with receptor proteins on localized neuronal cilia of ORNs. These dendritic extensions, cilia, express one type of protein receptor, although individual odorants can interact with multiple different receptor proteins. As new ORNs mature, they have decreased expression levels of multiple olfactory receptor genes , contrasting with mature ORNs firm rule of one neuron—one expressed olfactory receptor gene. Moreover, different odors activate specific ORNs in

1776-550: The nose are transported to the brain via olfactory nerve. This can be useful for nasal administration of medications. It can be harmful when the particles are soot or magnetite in air pollution . In naegleriasis , "brain-eating" amoeba enter through the olfactory mucosa of the nasal tissues and follow the olfactory nerve fibers into the olfactory bulbs and then the brain. Afferent nerve fiber Afferent nerve fibers are axons (nerve fibers) of sensory neurons that carry sensory information from sensory receptors to

1824-414: The olfactory bulb and from there they reach the olfactory areas of the brain via the olfactory tract . The olfactory nerve is the shortest of the twelve cranial nerves and, similar to the optic nerve, does not emanate from the brainstem . The olfaction system works to ensure that people can successfully identify an extensive range of odorants and distinguish odors from one another. Odorants interact with

1872-486: The olfactory epithelium and travel ipsilaterally to the olfactory bulb where the ORN axons coalesce into multiple clusters, called glomeruli , which together form the olfactory nerve. The ORN axons of each glomerulus synapse with apical dendrites of mitral cells , the primary projection neurons of the olfactory bulb, which create and send action potentials further into the CNS. ORNs directly interact with odorants inhaled into

1920-609: The olfactory epithelium which can also subject the ORNs to damage through continuous exposure to harmful substances such as airborne pollutants , microorganisms , and allergens . Therefore, ORNs maintain a normal cycle of degeneration and regeneration. The olfactory epithelium consists of three main cell types: supporting cells, mature ORNs, and basal cells. Regeneration of ORNs requires the division of basal cells, neural stem cells , to produce new receptor neurons. This regeneration process makes ORNs unique when compared to other neurons. In

1968-401: The olfactory nerve are not visible on a cadaver brain because they are severed upon removal. The specialized olfactory receptor neurons of the olfactory nerve are located in the olfactory mucosa of the upper parts of the nasal cavity . The olfactory nerves consist of a collection of many sensory nerve fibers that extend from the olfactory epithelium to the olfactory bulb , passing through

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2016-478: The outer surface of olfactory cilia within the olfactory epithelium . Odorant binding to the cilia of an ORN evokes an electrical response, kickstarting odor transduction. An individual ORN contains several microvilli , olfactory cilia, which protrude from a knoblike structure at the apical surface involved in dendritic processes . The olfactory cilia lack the cytoskeletal features of motile cilia and are, therefore, more similar to microvilli like that found in

2064-466: The relationship between afferent and efferent  : a fferent connection a rrives and an e fferent connection e xits . Another mnemonic device used for remembering afferent and efferent (in terms of the spinal cord, with its dorsal/ventral organization) is SAME DAVE. Sensory Afferent Motor Efferent, Dorsal Afferent Ventral Efferent. Afferent and efferent are connected to affect and effect through their common Latin roots: afferent nerves affect

2112-510: The structure onto a related archaeal CCA tRNA nucleotidyltransferase ( PDB : 1R89 ​) allows for assignment of the residues to specific functions: γ-phosphate binding, structural stabilization, DxD motif for metal ion binding, and finally ribose binding. These adenylyl cyclases are toxins secreted by pathogenic bacteria such as Bacillus anthracis , Bordetella pertussis , Pseudomonas aeruginosa , and Vibrio vulnificus during infections. These bacteria also secrete proteins that enable

2160-419: The subject, whereas efferent nerves allow the subject to effect change. Adenylate 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: It has key regulatory roles in essentially all cells . It

2208-421: The two aspartate residues on C1. They perform a nucleophilic attack of the 3'-OH group of the ribose on the α-phosphoryl group of ATP. The two lysine and aspartate residues on C2 selects ATP over GTP for the substrate, so that the enzyme is not a guanylyl cyclase. A pair of arginine and asparagine residues on C2 stabilizes the transition state. In many proteins, these residues are nevertheless mutated while retaining

2256-410: The upper part of the nasal cavity . From the olfactory mucosa, the nerve (actually many small nerve fascicles) travels up through the cribriform plate of the ethmoid bone to reach the surface of the brain. Here the fascicles enter the olfactory bulb and synapse there; from the bulbs (one on each side) the olfactory information is transmitted into the brain via the olfactory tract . The fascicles of

2304-498: Was discovered in Euglena gracilis and can be expressed in other organisms through genetic manipulation. Shining blue light on a cell containing PAC activates it and abruptly increases the rate of conversion of ATP to cAMP. This is a useful technique for researchers in neuroscience because it allows them to quickly increase the intracellular cAMP levels in particular neurons, and to study the effect of that increase in neural activity on

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