Dendrin is a neural and renal

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...

whose exact function is still relatively unclear; however, its location in the

brain The brain is an organ (biology), organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It consists of nervous tissue and is typically located in the head (cephalization), usually near organs for ...

and

kidney In humans, the kidneys are two reddish-brown bean-shaped blood-filtering organ (anatomy), organs that are a multilobar, multipapillary form of mammalian kidneys, usually without signs of external lobulation. They are located on the left and rig ...

s is well known as are some of the neural processes it affects. Within the brain, dendrin can be found in

neuron A neuron (American English), neurone (British English), or nerve cell, is an membrane potential#Cell excitability, excitable cell (biology), cell that fires electric signals called action potentials across a neural network (biology), neural net ...

s and is most notably associated with

sleep deprivation Sleep deprivation, also known as sleep insufficiency or sleeplessness, is the condition of not having adequate duration and/or quality of sleep to support decent alertness, performance, and health. It can be either Chronic (medicine), chronic ...

. Sleep deprivation causes some areas of the brain dendrin levels to increase, but this increase is insignificant and in total sleep deprivation causes a decrease of the

mRNA In molecular biology, messenger ribonucleic acid (mRNA) is a single-stranded molecule of RNA that corresponds to the genetic sequence of a gene, and is read by a ribosome in the process of Protein biosynthesis, synthesizing a protein. mRNA is ...

and protein form of dendrin. Along with two other proteins, MAGI/S-SCAM and α-actinin, dendrin is linked to

synaptic plasticity In neuroscience, synaptic plasticity is the ability of synapses to Chemical synapse#Synaptic strength, strengthen or weaken over time, in response to increases or decreases in their activity. Since memory, memories are postulated to be represent ...

and memory formation in the brain. Nicotine levels have also been shown to have an effect on dendrin expression in the brain. Although unlike sleep deprivation, nicotine increases overall dendrin level. Originally thought to be a brain specific protein, there is now evidence to suggest that dendrin is also found in the kidneys. Dendrin is used to detect glomerulopathy or renal disease, based on its location in the kidneys. Within the kidneys it also works to prevent urinary protein loss. Most studies and information on dendrin pertain specifically to rat or mice brains.

Structure

Dendrin has a similar structure in mice, rats, and humans. The protein is composed of 2,067

nucleotides Nucleotides are Organic compound, organic molecules composed of a nitrogenous base, a pentose sugar and a phosphate. They serve as monomeric units of the nucleic acid polymers – deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), both o ...

, is

hydrophilic A hydrophile is a molecule or other molecular entity that is attracted to water molecules and tends to be dissolved by water.Liddell, H.G. & Scott, R. (1940). ''A Greek-English Lexicon'' Oxford: Clarendon Press. In contrast, hydrophobes are n ...

, and is rich in the animo acid

proline Proline (symbol Pro or P) is an organic acid classed as a proteinogenic amino acid (used in the biosynthesis of proteins), although it does not contain the amino group but is rather a secondary amine. The secondary amine nitrogen is in the p ...

. Dendrin is a

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 f ...

substrate that is composed of multiple

consensus site A consensus site is a term in molecular biology that refers to a site on a protein that is often modified in a particular way. Modifications may be N- or O- linked glycosylation, phosphorylation, tyrosine sulfation In biochemistry, tyrosine sulf ...

s for

phosphorylation In biochemistry, phosphorylation is described as the "transfer of a phosphate group" from a donor to an acceptor. A common phosphorylating agent (phosphate donor) is ATP and a common family of acceptor are alcohols: : This equation can be writ ...

by protein kinase C, casein kinase 11, CAMP-dependent and proline-dependent kinases, and

tyrosine kinase A tyrosine kinase is an enzyme that can transfer a phosphate group from ATP to the tyrosine residues of specific proteins inside a cell. It functions as an "on" or "off" switch in many cellular functions. Tyrosine kinases belong to a larger cla ...

. Surprisingly, the protein structure does not have any

secondary structure Protein secondary structure is the local spatial conformation of the polypeptide backbone excluding the side chains. The two most common Protein structure#Secondary structure, secondary structural elements are alpha helix, alpha helices and beta ...

patterns, such as lengthy regions of α helices or β sheets. Appropriately named, dendrin in its

form is often found in the

dendrites A dendrite (from Greek δένδρον ''déndron'', "tree") or dendron is a branched cytoplasmic process that extends from a nerve cell that propagates the electrochemical stimulation received from other neural cells to the cell body, or soma ...

of neurons. The unique structure of dendrin allows it to participate in many different processes, such as

in the brain and disease detection in the kidneys.

Discovery

Dendrin was originally discovered in rat neurons and encoded by the brain specific transcript 464 by M. Neuner-Jehle. In 1996, 6 rats were tested using affinity-purified polyclonal rabbit anti-dendrin

antibodies An antibody (Ab) or immunoglobulin (Ig) is a large, Y-shaped protein belonging to the immunoglobulin superfamily which is used by the immune system to identify and neutralize antigens such as bacteria and viruses, including those that caus ...

. Using this technique two different proteins were identified one of which was dendrin. Dendrin expression was measured in sleep deprived rats and in control rats. Neuner-Jehle found that when the rats were sleep deprived, dendrin levels decreased. Neuner-Jehle also studied the location of dendrin expression by staining brain sections and was able to show the areas that were richest with dendrin. Most notably, the greatest protein was found in the

forebrain In the anatomy of the brain of vertebrates, the forebrain or prosencephalon is the rostral (forward-most) portion of the brain. The forebrain controls body temperature, reproductive functions, eating, sleeping, and the display of emotions. Ve ...

and

hippocampus The hippocampus (: hippocampi; via Latin from Ancient Greek, Greek , 'seahorse'), also hippocampus proper, is a major component of the brain of humans and many other vertebrates. In the human brain the hippocampus, the dentate gyrus, and the ...

. After this initial study, it was assumed that dendrin was located only in the brain.Neuner-Jehle, M., Denizot, J., Borbély, A., & Mallet, J. (1996). Characterization and sleep deprivation-induced expression modulation of dendrin, a novel dendritic protein in rat brain neurons. Journal of Neuroscience Research, 46(2), 138-151. However, in 2006, Kawata et al. found that the dendrin protein is also located in the kidneys. A yeast two-hybrid screening of kidney

cDNA In genetics, complementary DNA (cDNA) is DNA that was reverse transcribed (via reverse transcriptase) from an RNA (e.g., messenger RNA or microRNA). cDNA exists in both single-stranded and double-stranded forms and in both natural and engin ...

proved to find dendrin in the kidney

podocyte Podocytes are cells in Bowman's capsule in the kidneys that wrap around capillaries of the glomerulus. Podocytes make up the epithelial lining of Bowman's capsule, the third layer through which filtration of blood takes place. Bowman's capsule ...

s, where it connects to

cytoskeleton The cytoskeleton is a complex, dynamic network of interlinking protein filaments present in the cytoplasm of all cells, including those of bacteria and archaea. In eukaryotes, it extends from the cell nucleus to the cell membrane and is compos ...

proteins: S-S-SCAM and CIN85.

Location

It is now known that dendrin is found in the brain and kidneys, but it is not expressed everywhere in these two organs. Dendrin has only been found in a very specific part of the brain and specific parts of the kidneys. Within the brain, dendrin is normally found in the forebrain and

and in the kidneys, dendrin is normally found in the slit diaphragm and

podocytes Podocytes are cells in Bowman's capsule in the kidneys that wrap around capillaries of the glomerulus. Podocytes make up the epithelial lining of Bowman's capsule, the third layer through which filtration of blood takes place. Bowman's capsule ...

. It is believed that the location of this protein may directly affect its function, both in the brain and in the kidneys.

Brain

Dendrin is a

postsynaptic Chemical synapses are biological junctions through which neurons' signals can be sent to each other and to non-neuronal cells such as those in muscles or glands. Chemical synapses allow neurons to form circuits within the central nervous syste ...

proteinKawata, A., Lida, J., Ikeda, M., Sato, Y., Mori, H., Kansaku, A., . . . Hata, Y. (2006). CIN85 is localized at synapses and forms a complex with S-SCAM via Dendrin. Journal of Biochemistry, 139(5), 931-939. doi: 10.1093/jb/mvj105 that is found in the forebrain and hippocampus. Specifically in the forebrain, dendrin is found in the

cerebral cortex The cerebral cortex, also known as the cerebral mantle, is the outer layer of neural tissue of the cerebrum of the brain in humans and other mammals. It is the largest site of Neuron, neural integration in the central nervous system, and plays ...

and the subcortical forebrain plus midbrain areas (SFMA). Dendrin has yet to be found in other parts of the brain, but is very abundant in the parts of the brain where it is known to be expressed. Within these known locations in the brain, dendrin is associated with the

actin Actin is a family of globular multi-functional proteins that form microfilaments in the cytoskeleton, and the thin filaments in muscle fibrils. It is found in essentially all eukaryotic cells, where it may be present at a concentration of ...

. Dendrin is found in the neuron's cell body and its

dendrite A dendrite (from Ancient Greek language, Greek δένδρον ''déndron'', "tree") or dendron is a branched cytoplasmic process that extends from a nerve cell that propagates the neurotransmission, electrochemical stimulation received from oth ...

s.Herb, A., Wisden, W., Catania, M. V., Marechal, D., Dresse, A., & Seeburg, P. H. (1997). Prominent dendritic localization in forebrain neurons of a novel mRNA and its product, dendrin. Molecular and Cellular Neuroscience, 8(5), 367-374. doi: 10.1006/mcne.1996.0594 This is the part of the cell that helps it to retain its structure and move other molecules throughout the cell. MAGI/S-SCAM is a component of the

that is used to keep dendrin in the

cytoplasm The cytoplasm describes all the material within a eukaryotic or prokaryotic cell, enclosed by the cell membrane, including the organelles and excluding the nucleus in eukaryotic cells. The material inside the nucleus of a eukaryotic cell a ...

of a neuron, and prevents the protein from diffusing into the

nucleus Nucleus (: nuclei) is a Latin word for the seed inside a fruit. It most often refers to: *Atomic nucleus, the very dense central region of an atom *Cell nucleus, a central organelle of a eukaryotic cell, containing most of the cell's DNA Nucleu ...

. Because of this location in the neuron, it is thought that dendrin is involved in

retrograde signaling Retrograde signaling in biology is the process where a signal travels backwards from a target source to its original source. For example, the nucleus of a cell is the original source for creating signaling proteins. During retrograde signaling, in ...

from the

synapse In the nervous system, a synapse is a structure that allows a neuron (or nerve cell) to pass an electrical or chemical signal to another neuron or a target effector cell. Synapses can be classified as either chemical or electrical, depending o ...

to the nucleus. This form of signaling is the reverse of normal neural signaling so that instead of the signal passing from the nucleus to the synapse, is passes from the synapse to the nucleus.

Kidneys

Dendrin is also expressed during mouse glomerulogenesis. The protein is usually expressed during the early capillary loop stage of glomerulogenesis and creates a linear pattern on the epithelial side of these loops. In normal mature kidneys, dendrin is found only in the

near the slit diaphragm.Duner, F., Patrakka, J., Xiao, Z., Larsson, J., Vlamis-Gardikas, A., Pettersson, E., . . . Wernerson, A. (2008). Dendrin expression in glomerulogenesis and in human minimal change nephrotic syndrome. Nephrology Dialysis Transplantation, 23(8), 2504-2511. doi: 10.1093/ndt/gfn100

Podocyte Podocytes are cells in Bowman's capsule in the kidneys that wrap around capillaries of the glomerulus. Podocytes make up the epithelial lining of Bowman's capsule, the third layer through which filtration of blood takes place. Bowman's capsule ...

s are epithelia cells in the kidneys that do not readily divide and act as a barrier that prevent urinary protein loss. Dendrin interacts with S-SCAM (used in organization of synapses) and CIN85, two

scaffold protein In biology, scaffold proteins are crucial regulators of many key signalling pathways. Although scaffolds are not strictly defined in function, they are known to interact and/or bind with multiple members of a signalling pathway, tethering them in ...

s in the kidneys. Within this organ, dendrin's functions include the prevention of urinary protein loss and the formation of protein-protein interaction webs at

dendritic spine A dendritic spine (or spine) is a small membrane protrusion from a neuron's dendrite that typically receives input from a single axon at the synapse. Dendritic spines serve as a storage site for synaptic strength and help transmit electrical sign ...

Slit diaphragm

The slit diaphragm is a part of the kidneys that regulates renal

ultrafiltration Ultrafiltration (UF) is a variety of membrane filtration in which forces such as pressure or concentration gradients lead to a separation through a semipermeable membrane. Suspended solids and solutes of high molecular weight are retained in t ...

.Yaddanapudi, S., Altintas, M. M., Kistler, A. D., Fernandez, I., Moller, C. C., Wei, C. L., . . . Reiser, J. (2011). CD2AP in mouse and human podocytes controls a proteolytic program that regulates cytoskeletal structure and cellular survival. Journal of Clinical Investigation, 121(10), 3965-3980. doi: 10.1172/jci58552 Specifically, it is a part of the glomerular filter, which separates blood from urine. The slit diaphragm is very thin molecular sheet that mainly filters out plasma proteins and separates the glomerular

podocyte foot processes Podocytes are cells in Bowman's capsule in the kidneys that wrap around capillaries of the glomerulus. Podocytes make up the epithelial lining of Bowman's capsule, the third layer through which filtration of blood takes place. Bowman's capsule ...

.Grahammer, F., Schell, C., & Huber, T. B. (2013). Molecular understanding of the slit diaphragm. Pediatric Nephrology, 28(10), 1957-1962. doi: 10.1007/s00467-012-2375-6 The slit diaphragm is attached to the actin cytoskeleton of the cell. Dendrin associates regularly with the slit diaphragm because the dendrin protein is located in these podocytes.

Function

Although the exact function of dendrin is not known, there is a great deal of data to show what processes it contributes to and potentially regulates. Dendrin is normally affected by different behaviors. Most commonly studied in rats, dendrin is known to decrease with prolonged sleep deprivation and increase with acute

nicotine Nicotine is a natural product, naturally produced alkaloid in the nightshade family of plants (most predominantly in tobacco and ''Duboisia hopwoodii'') and is widely used recreational drug use, recreationally as a stimulant and anxiolytic. As ...

intake. Within the brain, dendrin interacts with α-actinin in postsynaptic dendritic spines. Together MAGI/S-SCAM, α-actinin, and dendrin form a tertiary complex at postsynaptic neural sites. This trio of proteins helps to connect a dense filamentous lattice (postsynaptic density or PSD) to the cytoskeleton of the spine and is also linked to synaptic plasticity and

memory Memory is the faculty of the mind by which data or information is encoded, stored, and retrieved when needed. It is the retention of information over time for the purpose of influencing future action. If past events could not be remembe ...

formation. Additionally, the protein binds to nephrin and CD2AP within the kidneys, where can help with intracellular signaling pathways. In conjunction with the slit diaphragm, dendrin helps to prevent urinary protein loss.Asanuma, K., Campbell, K. N., Kim, K., Faul, C., & Mundel, P. (2007). Nuclear relocation of the nephrin and CD2AP-binding protein dendrin promotes apoptosis of podocytes. Proceedings of the National Academy of Sciences of the United States of America, 104(24), 10134-10139. doi: 10.1073/pnas.0700917104

Sleep deprivation effect on dendrin

When dendrin was originally discovered, it was associated with

. Lack of sleep causes a decrease in dendrin

concentrations even after only 24 hours of no sleep. There is a slight increase in dendrin mRNA in the

caused by sleep deprivation although it is very minimal. Within the

, dendrin mRNA concentrations remain unchanged. Even though some dendrin levels in the brain rise or remain unchanged when sleep deprivation occurs, overall the levels of dendrin decrease. Through multiple studies it was found that there is a correlation between the levels of dendrin and sleep deprivation. Since it is still not clear what role dendrin plays in the brain, it is unclear how the processes dendrin is involved in are affected by lack of sleep.

Nicotine effect on dendrin

Dendrin mRNA levels are increased with

use in adolescent rat brains; however, these same levels of protein do not change in adults rats. It has also been shown that dendrin expression is not altered by

cocaine Cocaine is a tropane alkaloid and central nervous system stimulant, derived primarily from the leaves of two South American coca plants, ''Erythroxylum coca'' and ''Erythroxylum novogranatense, E. novogranatense'', which are cultivated a ...

or by placing the subject in a new or different environment. The proteins that dendrin typically associates with tend to be proteins that are linked to synaptic modification and learning. Expression of dendrin with even a small amount of nicotine could alter these processes and functions. Increased expression of dendrin caused by nicotine use is found mostly in the forebrain region of rats. Additional increase in dendrin mRNA is also found in the striatum.Schochet, T. L., Bremer, Q. Z., Brownfield, M. S., Kelley, A. E., & Landry, C. F. (2008). The dendritically targeted protein Dendrin is induced by acute nicotine in cortical regions of adolescent rat brain. European Journal of Neuroscience, 28(10), 1967-1979. doi: 10.1111/j.1460-9568.2008.06483.x

Synaptic plasticity

The protein trio of MAGI/S-SCAM, α-actinin, and dendrin helps to connect

postsynaptic density The postsynaptic density (PSD) is a protein dense ''specialization'' attached to the postsynaptic membrane. PSDs were originally identified by electron microscopy as an electron-dense region at the membrane of a postsynaptic neuron. The PSD is in ...

(PSD) to the cytoskeleton of the spine. The spatially restricted synthesis of dendrin contributes to the regulation of the synaptic

. The postsynaptic cytoskeleton, in turn, is involved in

and

formation suggesting that dendrin expression plays a role in these two brain functions.Kremerskothen, J., Kindler, S., Finger, I., & Barnekow, A. (2006). Postsynaptic recruitment of dendrin depends on both dendritic mrna transport and synaptic anchoring. Journal of Neurochemistry, 96, 1659-1666. doi: 10.1111/j.1471-4159.2006.03679.x If the synapse is damaged, this protein trio may play a role in its ability to regain function or the synaptic function to be taken over by another part of the brain. The involvement of dendrin in memory formation also suggests that external influences like sleep deprivation or nicotine consumption can alter or affect how memories are formed or stored.

Regulation of dendrin

Down-regulation In biochemistry, in the biological context of organisms' regulation of gene expression and production of gene products, downregulation is the process by which a cell decreases the production and quantities of its cellular components, such as RN ...

of dendrin is due to sleep deprivation which reduces the numbers of dendrin in the neuron. Sleep deprivation causes the most notable regulation and while it does not cause a decrease in dendrin mRNA and protein everywhere in the brain, the most significant change in dendrin levels is an overall decrease. Dendrin is regulated in the kidneys by CD2AP, which assists in dendrin movement to the nucleus of the

. This movement mainly occurs when an injury, or cell death occurs in the podocyte

epithelial Epithelium or epithelial tissue is a thin, continuous, protective layer of cells with little extracellular matrix. An example is the epidermis, the outermost layer of the skin. Epithelial ( mesothelial) tissues line the outer surfaces of man ...

cells.

Injury in the kidneys

When there is

glomerular ''Glomerulus'' (; : glomeruli) is a common term used in anatomy to describe globular structures of entwined vessels, fibers, or neurons. ''Glomerulus'' is the diminutive of the Latin ''glomus'', meaning "ball of yarn". ''Glomerulus'' may refer to ...

injury in the kidneys, the dendrin protein relocates to the podocyte nucleus in the slit diaphragm. The movement of this protein to the podocyte is associated with podocyte

apoptosis Apoptosis (from ) is a form of programmed cell death that occurs in multicellular organisms and in some eukaryotic, single-celled microorganisms such as yeast. Biochemistry, Biochemical events lead to characteristic cell changes (Morphology (biol ...

. There is proof that the action of a podocyte cell killing itself causes dendrin to move to the nucleus. Damage to the podocytes causes the silt diaphragm to collapse and

tight junction Tight junctions, also known as occluding junctions or ''zonulae occludentes'' (singular, ''zonula occludens''), are multiprotein Cell junction, junctional complexes between epithelial cells, sealing and preventing leakage of solutes and water. Th ...

s, or cell to cell connections to be formed. It has been shown that dendrin is involved in promoting apoptosis of the podocytes. Apoptosis leads to a decrease in podocyte

cells which causes

proteinuria Proteinuria is the presence of excess proteins in the urine. In healthy persons, urine contains very little protein, less than 150 mg/day; an excess is suggestive of illness. Excess protein in the urine often causes the urine to become fo ...

and could culminate in

glomerulosclerosis Glomerulosclerosis is the hardening of the glomeruli in the kidney. It is a general term to describe scarring of the kidneys' tiny blood vessels, the glomeruli, the functional units in the kidney that filter urea from the blood. Proteinuria (lar ...

. This relocation of dendrin can potentially help to diagnose any kidney damage or kidney disease. Dendrin locations in the kidneys can help determine the stage of

and how many podocytes have been lost to apoptosis.Asanuma, K., Akiba-Takagi, M., Kodama, F., Asao, R., Nagai, Y., Lydia, A., . . . Tomino, Y. (2011). Dendrin Location in Podocytes Is Associated with Disease Progression in Animal and Human Glomerulopathy. American Journal of Nephrology, 33(6), 537-549. doi: 10.1159/000327995

References

{{reflist Molecular neuroscience