Synaptojanin
Encyclopedia
Synaptojanin is a protein
involved in vesicle uncoating in neuron
s. This is an important regulatory lipid
phosphatase
. It dephosphorylate
s the D-5 position phosphate
from Phosphatidylinositol (3,4,5)-trisphosphate
(PIP3) and Phosphatidylinositol (4,5)-bisphosphate
(PIP2). It belongs to family of 5-phosphatases, which are structurally unrelated to D-3 inositol
phosphatases like PTEN
. Other members of the family of 5'phosphoinositide phosphatases include OCRL, SHIP1, SHIP2, INPP5J, INPP5E, INPP5B, INPP5A and SKIP.
. In general, vesicles containing neurotransmitters fuse with the presynaptic cell in order to release neurotransmitter into the synaptic cleft. It is the release of neurotransmitters that allows neuron to neuron communication in the nervous system. The recovery of the vesicle is referred to as endocytosis and is important to reset the presynaptic cell with new neurotransmitter.
Synaptojanin 1 and Synaptojanin 2 are the two main proteins in the synaptojanin family. Synaptojanin 2 can be further subdivided into synaptojanin 2a and synaptojanin 2b.
The mechanism by which vesicles are recovered is thought to involve the synaptojanin attracting the protein clathrin, which coats the vesicle and initiates vesicle endocytosis.
Synaptojanins are composed to three domains. The first is a central inositol 5-phosphatase domain, which can act on both PIP2 and PIP3. The second is an N-terminal Sac1-like inositol phosphatase domain, which can hydrolyze to PI in vitro PIP, PIP2. The third is a C-terminal domain that is rich in the amino acid proline and interacts with several proteins also involved in vesicle endocytosis . Specifically, the c-terminal domain interacts with amphiphysin, endophilin, DAP160/intersectin, syndapin and Eps15. The function of endophilin appears to be a binding partner for synaptojanin such that it can interact with other proteins and is involved in the initiation of shallow clathrin coated pits. Dap160 is a molecular scaffolding protein and functions in actin recruitment. Dynamin is a GTPase involved in vesicle budding, specifically modulating the severance of the vesicle from the neuronal membrane. Dynamin appears to be playing a larger role in neurite formation because its vesicle pinching role and the possibility of it recycling plasma membrane and growth factor receptor proteins
. However the actual extension of the neurite involves the insertion of membrane lipids immediately behind the growth one. In fact, membranes can be trafficked from degenerating extensions to elongating ones. Synaptojanin has been proposed as the mechanism by which membrane lipids can be trafficked around the developing neuron
. This trafficking involves vesicle endocytosis. In the presence of nerve growth factor (NGF), TrkA receptors are trafficked to the stimulated side of the growth cone. Additionally, calcium and glutamate stimulate the trafficking of AMPA receptors to the stimulated side of the growth cone. Both of these receptors are trafficked via synaptojanin.
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
involved in vesicle uncoating in neuron
Neuron
A 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. This is an important regulatory lipid
Lipid
Lipids constitute a broad group of naturally occurring molecules that include fats, waxes, sterols, fat-soluble vitamins , monoglycerides, diglycerides, triglycerides, phospholipids, and others...
phosphatase
Phosphatase
A phosphatase is an enzyme that removes a phosphate group from its substrate by hydrolysing phosphoric acid monoesters into a phosphate ion and a molecule with a free hydroxyl group . This action is directly opposite to that of phosphorylases and kinases, which attach phosphate groups to their...
. It dephosphorylate
Dephosphorylation
Dephosphorylation is the essential process of removing phosphate groups from an organic compound by hydrolysis. Its opposite is phosphorylation...
s the D-5 position phosphate
Phosphate
A phosphate, an inorganic chemical, is a salt of phosphoric acid. In organic chemistry, a phosphate, or organophosphate, is an ester of phosphoric acid. Organic phosphates are important in biochemistry and biogeochemistry or ecology. Inorganic phosphates are mined to obtain phosphorus for use in...
from Phosphatidylinositol (3,4,5)-trisphosphate
Phosphatidylinositol (3,4,5)-trisphosphate
Phosphatidylinositol -triphosphate , abbreviated PIP3, is the product of the class I phosphoinositide 3-kinases phosphorylation on phosphatidylinositol -bisphosphate .-Discovery:...
(PIP3) and Phosphatidylinositol (4,5)-bisphosphate
Phosphatidylinositol (4,5)-bisphosphate
Phosphatidylinositol 4,5-bisphosphate or PtdInsP2, also known simply as PIP2, is a minor phospholipid component of cell membranes...
(PIP2). It belongs to family of 5-phosphatases, which are structurally unrelated to D-3 inositol
Inositol
Inositol or cyclohexane-1,2,3,4,5,6-hexol is a chemical compound with formula 6126 or 6, a sixfold alcohol of cyclohexane. It exists in nine possible stereoisomers, of which the most prominent form, widely occurring in nature, is cis-1,2,3,5-trans-4,6-cyclohexanehexol, or myo-inositol...
phosphatases like PTEN
PTEN (gene)
Phosphatase and tensin homolog is a protein that, in humans, is encoded by the PTEN gene. Mutations of this gene are a step in the development of many cancers....
. Other members of the family of 5'phosphoinositide phosphatases include OCRL, SHIP1, SHIP2, INPP5J, INPP5E, INPP5B, INPP5A and SKIP.
Synaptojanin Family
The synaptojanin family comprises proteins that are key players in the synaptic vesicle recovery at the synapseSynapse
In the nervous system, a synapse is a structure that permits a neuron to pass an electrical or chemical signal to another cell...
. In general, vesicles containing neurotransmitters fuse with the presynaptic cell in order to release neurotransmitter into the synaptic cleft. It is the release of neurotransmitters that allows neuron to neuron communication in the nervous system. The recovery of the vesicle is referred to as endocytosis and is important to reset the presynaptic cell with new neurotransmitter.
Synaptojanin 1 and Synaptojanin 2 are the two main proteins in the synaptojanin family. Synaptojanin 2 can be further subdivided into synaptojanin 2a and synaptojanin 2b.
The mechanism by which vesicles are recovered is thought to involve the synaptojanin attracting the protein clathrin, which coats the vesicle and initiates vesicle endocytosis.
Synaptojanins are composed to three domains. The first is a central inositol 5-phosphatase domain, which can act on both PIP2 and PIP3. The second is an N-terminal Sac1-like inositol phosphatase domain, which can hydrolyze to PI in vitro PIP, PIP2. The third is a C-terminal domain that is rich in the amino acid proline and interacts with several proteins also involved in vesicle endocytosis . Specifically, the c-terminal domain interacts with amphiphysin, endophilin, DAP160/intersectin, syndapin and Eps15. The function of endophilin appears to be a binding partner for synaptojanin such that it can interact with other proteins and is involved in the initiation of shallow clathrin coated pits. Dap160 is a molecular scaffolding protein and functions in actin recruitment. Dynamin is a GTPase involved in vesicle budding, specifically modulating the severance of the vesicle from the neuronal membrane. Dynamin appears to be playing a larger role in neurite formation because its vesicle pinching role and the possibility of it recycling plasma membrane and growth factor receptor proteins
Role in Development
Synaptojanin, through its interactions with a variety of proteins and molecules is thought to play a role in the development of nervous systems.Ephrin
Synaptojanin 1 has been found to be influenced by the protein ephrin. Ephrin is a chemorepulsant meaning that its interactions with proteins results in an inactivation or retraction of processes when referring to neuronal migration. Ephrin's receptor is called Eph and is a receptor tyrosine kinase Upon activation of the Eph receptor, synaptojanin 1 becomes phosphorylated at the proline rich domain and is inhibited from binding with any of its natural binding partners. Therefore, the presence of ephrin inactivates vesicle endocytosis.Calcium
The influx of calcium in the neuron has been shown to activate a variety of molecules including some calcium dependent phosphatases that activate synaptojanin.Membranes
Neuronal migration during development involves the extension of a neurite along the extracellular matrix. This extension is guided by the growth coneGrowth cone
A growth cone is a dynamic, actin-supported extension of a developing axon seeking its synaptic target. Their existence was originally proposed by Spanish histologist Santiago Ramón y Cajal based upon stationary images he observed under the microscope...
. However the actual extension of the neurite involves the insertion of membrane lipids immediately behind the growth one. In fact, membranes can be trafficked from degenerating extensions to elongating ones. Synaptojanin has been proposed as the mechanism by which membrane lipids can be trafficked around the developing neuron
Receptors
During development, receptors are trafficked around the growth coneGrowth cone
A growth cone is a dynamic, actin-supported extension of a developing axon seeking its synaptic target. Their existence was originally proposed by Spanish histologist Santiago Ramón y Cajal based upon stationary images he observed under the microscope...
. This trafficking involves vesicle endocytosis. In the presence of nerve growth factor (NGF), TrkA receptors are trafficked to the stimulated side of the growth cone. Additionally, calcium and glutamate stimulate the trafficking of AMPA receptors to the stimulated side of the growth cone. Both of these receptors are trafficked via synaptojanin.