Podocytes
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Podocytes are
cells Cell most often refers to: * Cell (biology), the functional basic unit of life Cell may also refer to: Locations * Monastic cell, a small room, hut, or cave in which a religious recluse lives, alternatively the small precursor of a monastery w ...
in
Bowman's capsule Bowman's capsule (or the Bowman capsule, capsula glomeruli, or glomerular capsule) is a cup-like sac at the beginning of the tubular component of a nephron in the mammalian kidney that performs the first step in the filtration of blood to form u ...
in the
kidney The kidneys are two reddish-brown bean-shaped organs found in vertebrates. They are located on the left and right in the retroperitoneal space, and in adult humans are about in length. They receive blood from the paired renal arteries; blo ...
s that wrap around
capillaries A capillary is a small blood vessel from 5 to 10 micrometres (μm) in diameter. Capillaries are composed of only the tunica intima, consisting of a thin wall of simple squamous endothelial cells. They are the smallest blood vessels in the body: ...
of the glomerulus. Podocytes make up the epithelial lining of Bowman's capsule, the third layer through which
filtration Filtration is a physical separation process that separates solid matter and fluid from a mixture using a ''filter medium'' that has a complex structure through which only the fluid can pass. Solid particles that cannot pass through the filter ...
of blood takes place. Bowman's capsule filters the
blood Blood is a body fluid in the circulatory system of humans and other vertebrates that delivers necessary substances such as nutrients and oxygen to the cells, and transports metabolic waste products away from those same cells. Blood in the cir ...
, retaining large
molecule A molecule is a group of two or more atoms held together by attractive forces known as chemical bonds; depending on context, the term may or may not include ions which satisfy this criterion. In quantum physics, organic chemistry, and b ...
s such as
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, res ...
s while smaller molecules such as
water Water (chemical formula ) is an inorganic, transparent, tasteless, odorless, and nearly colorless chemical substance, which is the main constituent of Earth's hydrosphere and the fluids of all known living organisms (in which it acts as ...
,
salts In chemistry, a salt is a chemical compound consisting of an ionic assembly of positively charged cations and negatively charged anions, which results in a compound with no net electric charge. A common example is table salt, with positively c ...
, and
sugar Sugar is the generic name for sweet-tasting, soluble carbohydrates, many of which are used in food. Simple sugars, also called monosaccharides, include glucose, fructose, and galactose. Compound sugars, also called disaccharides or do ...
s are filtered as the first step in the formation of
urine Urine is a liquid by-product of metabolism in humans and in many other animals. Urine flows from the kidneys through the ureters to the urinary bladder. Urination results in urine being excreted from the body through the urethra. Cellul ...
. Although various
viscera In biology, an organ is a collection of tissues joined in a structural unit to serve a common function. In the hierarchy of life, an organ lies between tissue and an organ system. Tissues are formed from same type cells to act together in a f ...
have
epithelial Epithelium or epithelial tissue is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. It is a thin, continuous, protective layer of compactly packed cells with a little intercellu ...
layers, the name visceral epithelial cells usually refers specifically to podocytes, which are specialized epithelial cells that reside in the visceral layer of the capsule. One type of specialized epithelial cell is
podocalyxin Podocalyxin, a sialoglycoprotein, is thought to be the major constituent of the glycocalyx of podocytes in the glomerulus (Bowman's capsule) in the kidneys. It is a member of the CD34 family of transmembrane sialomucins. It coats the secondary foo ...
. The podocytes have long foot processes called ''pedicels'', for which the cells are named (''
podo- This is a list of common affixes used when scientifically naming species, particularly extinct species for whom only their scientific names are used, along with their derivations. *a-, an-: ''Pronunciation'': /ə/, /a/, /ən/, /an/. ''Origin'' ...
'' + '' -cyte''). The pedicels wrap around the capillaries and leave slits between them. Blood is filtered through these slits, each known as a filtration slit, slit diaphragm, or slit pore. Several proteins are required for the pedicels to wrap around the capillaries and function. When infants are born with certain defects in these proteins, such as
nephrin Nephrin is a protein necessary for the proper functioning of the renal filtration barrier. The renal filtration barrier consists of fenestrated endothelial cells, the glomerular basement membrane, and the podocytes of epithelial cells. Nephrin is ...
and
CD2AP CD2-associated protein is a protein that in humans is encoded by the ''CD2AP'' gene. Function This gene encodes a scaffolding molecule that regulates the actin cytoskeleton. The protein directly interacts with filamentous actin and a variety o ...
, their kidneys cannot function. People have variations in these proteins, and some variations may predispose them to
kidney failure Kidney failure, also known as end-stage kidney disease, is a medical condition in which the kidneys can no longer adequately filter waste products from the blood, functioning at less than 15% of normal levels. Kidney failure is classified as eit ...
later in life.
Nephrin Nephrin is a protein necessary for the proper functioning of the renal filtration barrier. The renal filtration barrier consists of fenestrated endothelial cells, the glomerular basement membrane, and the podocytes of epithelial cells. Nephrin is ...
is a
zipper A zipper, zip, fly, or zip fastener, formerly known as a clasp locker, is a commonly used device for binding together two edges of fabric or other flexible material. Used in clothing (e.g. jackets and jeans), luggage and other bags, camping ...
-like protein that forms the slit diaphragm, with spaces between the teeth of the zipper big enough to allow sugar and water through but too small to allow proteins through. Nephrin defects are responsible for congenital kidney failure. CD2AP regulates the podocyte cytoskeleton and stabilizes the slit diaphragm.


Structure

Podocytes are found lining the Bowman's capsules in the nephrons of the kidney. The foot processes known as ''pedicels'' that extend from the podocytes wrap themselves around the
capillaries A capillary is a small blood vessel from 5 to 10 micrometres (μm) in diameter. Capillaries are composed of only the tunica intima, consisting of a thin wall of simple squamous endothelial cells. They are the smallest blood vessels in the body: ...
of the glomerulus to form the filtration slits. The pedicels increase the surface area of the cells enabling efficient
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 the ...
. Podocytes secrete and maintain the
basement membrane The basement membrane is a thin, pliable sheet-like type of extracellular matrix that provides cell and tissue support and acts as a platform for complex signalling. The basement membrane sits between epithelial tissues including mesothelium an ...
. There are numerous coated
vesicles Vesicle may refer to: ; In cellular biology or chemistry * Vesicle (biology and chemistry), a supramolecular assembly of lipid molecules, like a cell membrane * Synaptic vesicle ; In human embryology * Vesicle (embryology), bulge-like features o ...
and coated pits along the basolateral domain of the podocytes which indicate a high rate of vesicular traffic. Podocytes possess a well-developed
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 ...
and a large
Golgi apparatus The Golgi apparatus (), also known as the Golgi complex, Golgi body, or simply the Golgi, is an organelle found in most eukaryotic cells. Part of the endomembrane system in the cytoplasm, it packages proteins into membrane-bound vesicles i ...
, indicative of a high capacity for
protein synthesis Protein biosynthesis (or protein synthesis) is a core biological process, occurring inside cells, balancing the loss of cellular proteins (via degradation or export) through the production of new proteins. Proteins perform a number of critical ...
and
post-translational modification Post-translational modification (PTM) is the covalent and generally enzymatic modification of proteins following protein biosynthesis. This process occurs in the endoplasmic reticulum and the golgi apparatus. Proteins are synthesized by ribo ...
s. There is also growing evidence of a large number of multivesicular bodies and other lysosomal components seen in these cells, indicating a high
endocytic Endocytosis is a cellular process in which substances are brought into the cell. The material to be internalized is surrounded by an area of cell membrane, which then buds off inside the cell to form a vesicle containing the ingested material. ...
activity.


Function

Podocytes have primary processes called trabeculae, which wrap around the glomerular capillaries. The trabeculae in turn have secondary processes called pedicels. Pedicels interdigitate, thereby giving rise to thin gaps called filtration slits. The slits are covered by slit diaphragms which are composed of a number of cell-surface proteins including
nephrin Nephrin is a protein necessary for the proper functioning of the renal filtration barrier. The renal filtration barrier consists of fenestrated endothelial cells, the glomerular basement membrane, and the podocytes of epithelial cells. Nephrin is ...
,
podocalyxin Podocalyxin, a sialoglycoprotein, is thought to be the major constituent of the glycocalyx of podocytes in the glomerulus (Bowman's capsule) in the kidneys. It is a member of the CD34 family of transmembrane sialomucins. It coats the secondary foo ...
, and P-cadherin, which restrict the passage of large
macromolecules A macromolecule is a very large molecule important to biophysical processes, such as a protein or nucleic acid. It is composed of thousands of covalently bonded atoms. Many macromolecules are polymers of smaller molecules called monomers. The ...
such as serum albumin and
gamma globulin Gamma globulins are a class of globulins, identified by their position after serum protein electrophoresis. The most significant gamma globulins are immunoglobulins (antibodies), although some immunoglobulins are not gamma globulins, and some g ...
and ensure that they remain in the bloodstream. Proteins that are required for the correct function of the slit diaphragm include
nephrin Nephrin is a protein necessary for the proper functioning of the renal filtration barrier. The renal filtration barrier consists of fenestrated endothelial cells, the glomerular basement membrane, and the podocytes of epithelial cells. Nephrin is ...
, NEPH1, NEPH2,
podocin Podocin is a protein component of the filtration slits of podocytes. Glomerular capillary endothelial cells, the glomerular basement membrane and the filtration slits function as the filtration barrier of the kidney glomerulus. Mutations in the ...
,
CD2AP CD2-associated protein is a protein that in humans is encoded by the ''CD2AP'' gene. Function This gene encodes a scaffolding molecule that regulates the actin cytoskeleton. The protein directly interacts with filamentous actin and a variety o ...
. and
FAT1 Protocadherin FAT1 is a protein that in humans is encoded by the ''FAT1'' gene. Function This gene is an ortholog of the ''Drosophila'' fat gene, which encodes a tumor suppressor essential for controlling cell proliferation during Drosophila d ...
. Small molecules such as
water Water (chemical formula ) is an inorganic, transparent, tasteless, odorless, and nearly colorless chemical substance, which is the main constituent of Earth's hydrosphere and the fluids of all known living organisms (in which it acts as ...
,
glucose Glucose is a simple sugar with the molecular formula . Glucose is overall the most abundant monosaccharide, a subcategory of carbohydrates. Glucose is mainly made by plants and most algae during photosynthesis from water and carbon dioxide, u ...
, and ionic salts are able to pass through the filtration slits and form an
ultrafiltrate 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 the ...
in the
tubular fluid Tubular fluid is the fluid in the tubules of the kidney. It starts as a renal ultrafiltrate in the glomerulus, changes composition through the nephron, and ends up as urine leaving through the ureters. Composition table The composition of tubular ...
, which is further processed by the
nephron The nephron is the minute or microscopic structural and functional unit of the kidney. It is composed of a renal corpuscle and a renal tubule. The renal corpuscle consists of a tuft of capillaries called a glomerulus and a cup-shaped structure ...
to produce
urine Urine is a liquid by-product of metabolism in humans and in many other animals. Urine flows from the kidneys through the ureters to the urinary bladder. Urination results in urine being excreted from the body through the urethra. Cellul ...
. Podocytes are also involved in regulation of
glomerular filtration rate Renal functions include maintaining an acid–base balance; regulating fluid balance; regulating sodium, potassium, and other electrolytes; clearing toxins; absorption of glucose, amino acids, and other small molecules; regulation of blood pre ...
(GFR). When podocytes contract, they cause closure of filtration slits. This decreases the GFR by reducing the surface area available for filtration.


Clinical significance

A loss of the foot processes of the podocytes (i.e., podocyte effacement) is a hallmark of minimal change disease, which has therefore sometimes been called foot process disease. Disruption of the filtration slits or destruction of the podocytes can lead to massive
proteinuria Proteinuria is the presence of excess proteins in the urine. In healthy persons, urine contains very little protein; an excess is suggestive of illness. Excess protein in the urine often causes the urine to become foamy (although this symptom ma ...
, where large amounts of protein are lost from the blood. An example of this occurs in the congenital disorder Finnish-type nephrosis, which is characterised by neonatal proteinuria leading to end-stage
kidney failure Kidney failure, also known as end-stage kidney disease, is a medical condition in which the kidneys can no longer adequately filter waste products from the blood, functioning at less than 15% of normal levels. Kidney failure is classified as eit ...
. This disease has been found to be caused by a mutation in the
nephrin Nephrin is a protein necessary for the proper functioning of the renal filtration barrier. The renal filtration barrier consists of fenestrated endothelial cells, the glomerular basement membrane, and the podocytes of epithelial cells. Nephrin is ...
gene. Presence of podocytes in urine has been proposed as an early diagnostic marker for
preeclampsia Pre-eclampsia is a disorder of pregnancy characterized by the onset of high blood pressure and often a significant amount of protein in the urine. When it arises, the condition begins after 20 weeks of pregnancy. In severe cases of the disease ...
.


See also

*
List of human cell types derived from the germ layers This is a list of cells in humans derived from the three embryonic germ layers – ectoderm, mesoderm, and endoderm. Cells derived from ectoderm Surface ectoderm Skin * Trichocyte * Keratinocyte Anterior pituitary * Gonadotrope * Corti ...


References


External links

* - "Mammal, renal vasculature (EM, High) * - ". Ultrastructure of the Cell: podocytes and glomerular capillaries" *
podocyte.ca
at Samuel Lunenfeld Research Institute * * * {{Kidney Kidney anatomy Human cells Epithelial cells