Dynamin
Encyclopedia
Dynamin is a GTPase
responsible for endocytosis
in the eukaryotic cell. Dynamins are principally involved in the scission of newly formed vesicles
from the membrane of one cellular compartment and their targeting to, and fusion with, another compartment, both at the cell surface (particularly caveolae
internalization) as well as at the Golgi apparatus
. Dynamin also plays a role in many processes including division of organelle
s, cytokinesis
and microbial pathogen
resistance.
Dynamin is part of the "Dynamin Superfamily," which includes classical dynamins, dynamin-like proteins, Mx proteins, OPA, mitofusins, and GBPs. Dynamin itself is a 96 kDa enzyme
, and was first isolated when researchers were attempting to isolate new microtubule
-based motors from the bovine brain. Dynamin has been extensively studied within clathrin
-coated vesicle budding from the cell membrane
.
To view the effect of GTP and GDP on dynamin spirals, follow this link: http://dynamin.niddk.nih.gov/figure2.html. In part A of this picture we see dynamin tubes in the absence of GTP; they are large and relaxed. In part B of the picture we see the same dynamin tubes from part one but after addition of GTP, GTP is hydrolysed because of intrinsic GTPase activity and constriction ensues. This is how dynamin works to pinch vesicles off from the membrane.
To view a ‘cartoon’ image of the non-constricted and constricted state of dynamin spirals, please follow this link: http://dynamin.niddk.nih.gov/figure5.html. The first structure on the left is dynamin in its relaxed state. The structure on the right is dynamin in its constricted state. This allows you to see how much dynamin tightens and changes when GTP is converted to GDP.
This constriction is in part the result of the twisting activity of dynamin This twisting is strictly dependent on its GTPase activity. Dynamin is the only molecular motor known to have a twisting activity. Dynamin is a right-handed helix, and has a right-handed twisting activity that explains its tightening and the pitch reduction described above.
have been found to cause dominant intermediate Charcot-Marie-Tooth disease
.
GTPase
GTPases are a large family of hydrolase enzymes that can bind and hydrolyze guanosine triphosphate . The GTP binding and hydrolysis takes place in the highly conserved G domain common to all GTPases.-Functions:...
responsible for endocytosis
Endocytosis
Endocytosis is a process by which cells absorb molecules by engulfing them. It is used by all cells of the body because most substances important to them are large polar molecules that cannot pass through the hydrophobic plasma or cell membrane...
in the eukaryotic cell. Dynamins are principally involved in the scission of newly formed vesicles
Vesicle (biology)
A vesicle is a bubble of liquid within another liquid, a supramolecular assembly made up of many different molecules. More technically, a vesicle is a small membrane-enclosed sack that can store or transport substances. Vesicles can form naturally because of the properties of lipid membranes , or...
from the membrane of one cellular compartment and their targeting to, and fusion with, another compartment, both at the cell surface (particularly caveolae
Caveolae
In biology, caveolae , which are a special type of lipid raft, are small invaginations of the plasma membrane in many vertebrate cell types, especially in endothelial cells and adipocytes....
internalization) as well as at the Golgi apparatus
Golgi apparatus
The Golgi apparatus is an organelle found in most eukaryotic cells. It was identified in 1898 by the Italian physician Camillo Golgi, after whom the Golgi apparatus is named....
. Dynamin also plays a role in many processes including division of organelle
Organelle
In cell biology, an organelle is a specialized subunit within a cell that has a specific function, and is usually separately enclosed within its own lipid bilayer....
s, cytokinesis
Cytokinesis
Cytokinesis is the process in which the cytoplasm of a single eukaryotic cell is divided to form two daughter cells. It usually initiates during the late stages of mitosis, and sometimes meiosis, splitting a binucleate cell in two, to ensure that chromosome number is maintained from one generation...
and microbial pathogen
Pathogen
A pathogen gignomai "I give birth to") or infectious agent — colloquially, a germ — is a microbe or microorganism such as a virus, bacterium, prion, or fungus that causes disease in its animal or plant host...
resistance.
Dynamin is part of the "Dynamin Superfamily," which includes classical dynamins, dynamin-like proteins, Mx proteins, OPA, mitofusins, and GBPs. Dynamin itself is a 96 kDa enzyme
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
, and was first isolated when researchers were attempting to isolate new microtubule
Microtubule
Microtubules are a component of the cytoskeleton. These rope-like polymers of tubulin can grow as long as 25 micrometers and are highly dynamic. The outer diameter of microtubule is about 25 nm. Microtubules are important for maintaining cell structure, providing platforms for intracellular...
-based motors from the bovine brain. Dynamin has been extensively studied within clathrin
Clathrin
Clathrin is a protein that plays a major role in the formation of coated vesicles. Clathrin was first isolated and named by Barbara Pearse in 1975. It forms a triskelion shape composed of three clathrin heavy chains and three light chains. When the triskelia interact they form a polyhedral lattice...
-coated vesicle budding from the cell membrane
Cell membrane
The cell membrane or plasma membrane is a biological membrane that separates the interior of all cells from the outside environment. The cell membrane is selectively permeable to ions and organic molecules and controls the movement of substances in and out of cells. It basically protects the cell...
.
Function
As a vesicle invaginates, dynamin forms a spiral around the neck of the vesicle. Once the spiral is in place, it extends lengthwise and constricts through GTP hydrolysis. This lengthening and tightening of the coil around the vesicle neck causes it to break and results in the pinching off of the vesicle from the parent membrane. An example of a vesicle is a clathrin-coated pit.To view the effect of GTP and GDP on dynamin spirals, follow this link: http://dynamin.niddk.nih.gov/figure2.html. In part A of this picture we see dynamin tubes in the absence of GTP; they are large and relaxed. In part B of the picture we see the same dynamin tubes from part one but after addition of GTP, GTP is hydrolysed because of intrinsic GTPase activity and constriction ensues. This is how dynamin works to pinch vesicles off from the membrane.
To view a ‘cartoon’ image of the non-constricted and constricted state of dynamin spirals, please follow this link: http://dynamin.niddk.nih.gov/figure5.html. The first structure on the left is dynamin in its relaxed state. The structure on the right is dynamin in its constricted state. This allows you to see how much dynamin tightens and changes when GTP is converted to GDP.
This constriction is in part the result of the twisting activity of dynamin This twisting is strictly dependent on its GTPase activity. Dynamin is the only molecular motor known to have a twisting activity. Dynamin is a right-handed helix, and has a right-handed twisting activity that explains its tightening and the pitch reduction described above.
Types
In mammals, three different dynamin genes have been identified.- Dynamin IIDNM2Dynamin-2 is a protein that in humans is encoded by the DNM2 gene.-Interactions:DNM2 has been shown to interact with SNX9, SHANK1 and SHANK2.-External Links:* -Further reading:...
is expressed in most cell types; - Dynamin IDNM1Dynamin-1 is a protein that in humans is encoded by the DNM1 gene.-Interactions:DNM1 has been shown to interact with Amphiphysin, FNBP1, NCK1, PACSIN1, Grb2 and SH3GL2.-Further reading:...
is expressed in neuronNeuronA neuron is an electrically excitable cell that processes and transmits information by electrical and chemical signaling. Chemical signaling occurs via synapses, specialized connections with other cells. Neurons connect to each other to form networks. Neurons are the core components of the nervous...
s and neuroendocrine cellNeuroendocrine cellNeuroendocrine cells are cells that receive neuronal input and, as a consequence of this input, release message molecules to the blood. In this way they bring about an integration between the nervous system and the endocrine system, a process known as neuroendocrine integration...
s - Dynamin IIIDNM3Dynamin-3 is a protein that in humans is encoded by the DNM3 gene. The protein encoded by this gene is a member of the dynamin family which possess mechanochemical properties involved in actin-membrane processes, predominantly in membrane budding. DNM3 is upregulated in Sézary's syndrome.-Further...
is strongly expressed in the testis, but is also present in heartHeartThe heart is a myogenic muscular organ found in all animals with a circulatory system , that is responsible for pumping blood throughout the blood vessels by repeated, rhythmic contractions...
, brainBrainThe brain is the center of the nervous system in all vertebrate and most invertebrate animals—only a few primitive invertebrates such as sponges, jellyfish, sea squirts and starfishes do not have one. It is located in the head, usually close to primary sensory apparatus such as vision, hearing,...
, and lungLungThe lung is the essential respiration organ in many air-breathing animals, including most tetrapods, a few fish and a few snails. In mammals and the more complex life forms, the two lungs are located near the backbone on either side of the heart...
tissue.
Disease implications
Mutations in Dynamin IIDNM2
Dynamin-2 is a protein that in humans is encoded by the DNM2 gene.-Interactions:DNM2 has been shown to interact with SNX9, SHANK1 and SHANK2.-External Links:* -Further reading:...
have been found to cause dominant intermediate Charcot-Marie-Tooth disease
Charcot-Marie-Tooth disease
Charcot–Marie–Tooth disease- , known also as Morbus Charcot-Marie-Tooth, Charcot-Marie-Tooth neuropathy, hereditary motor and sensory neuropathy , hereditary sensorimotor neuropathy , or peroneal muscular atrophy, is an inherited disorder of nerves that takes different forms...
.