Here we use microarray gene profiling and electron microscop......
Here we use microarray gene profiling and electron microscopic stereology to reveal lower expression of synaptic-function-related genes (CALM2, SYN1, RAB3A, RAB4B and TUBB4) in the dlPFC of subjects with MDD and a corresponding lower number of synapses. We also identify a transcriptional repressor, GATA1, expression of which is higher in MDD More...
Positive relationships between RAB3A and other components at different levels (count: 0)
Positive relationship network of RAB3A in MK4MDD
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Note:
1. The different color of the nodes denotes the level of the nodes.
Genetic/Epigenetic Locus
Protein and Other Molecule
Cell and Molecular Pathway
Neural System
Cognition and Behavior
Symptoms and Signs
Environment
MDD
2. Besides the component related relationships from literature, gene mapped protein and protein mapped gene are also shown in the network.
If the mapped gene or protein is not from literature, square node would be used instead of Circle node.
Accordingly, the relationship is marked with dot line.
2. User can drag the nodes to rearrange the layout of the network. Click the node will enter the report page of the node.
Right-click will show also the menus to link to the report page of the node and remove the node and related edges.
Hover the node will show the level of the node and hover the edge will show the evidence/description of the edge.
3. The network is generated using Cytoscape Web
Negative relationships between RAB3A and MDD (count: 0)
Negative relationships between RAB3A and other components at different levels (count: 0)
Rab GTPases Mark Targets In The Endocytotic Machinery
The eukaryotic cell contains compartments with distinct func......
The eukaryotic cell contains compartments with distinct functions bounded by lipid bilayer membranes. The movement of membrane vesicles between these compartments allows proteins in the secretory pathway to move outward from the endoplasmic reticulum (ER) to the Golgi, trans Golgi network (TGN), secretory vesicles, and the plasma membrane and to be secreted into the extracellular environment. The trafficking of membrane vesicles is also essential for endocytosis and the movement of material from the extracellular environment into the early endosome (EE), late endosome (LE) and lysosome. The movement of vesicles and their contents between these compartments and their secretion are essential for a host of cellular functions, including the release of neurotransmitters and hormones. The movement of membrane vesicles between all of these compartments is regulated by members of the Rab family of GTPases, part of the ras superfamily of genes, regulated through binding of GTP and hydrolysis of bound GTP to GDP. At least eleven yeast genes in this family have been identified as Ypts, yeast transport proteins, and over sixty mammalian Rab genes have been identified in this highly conserved gene family. The products of the Rab genes regulate specific steps in vesicle transport. Rab1 is involved in the movement of membranes from the ER through the Golgi. Rab3 regulates secretory vesicle release and Rab27 is also involved in regulated release of secreted proteins. Rab5, 7 and 9 contribute to endocytosis while Rab4 and Rab11 mediate recycling from the endosome back to the plasma membrane. Rab11 is involved in both endocytosis and exocytosis. As with other Ras family GTPases, the activity of Rabs is regulated by guanine-nucleotide exchange factors (GEFs) and GAPs (GTPase activating proteins). Downstream effectors must also interact with Rabs to transmit their signals regulating each step of the membrane trafficking pathways including vesicle formation, movement of vesicles between compartments, vesicle docking, fusion and membrane remodeling. Downstream effectors of the Rabs include Rabphilin-3 (vesicle movement effector for Rab3), Rabphilin-11 (vesicle formation effector for Rab11), and EEA1 (vesicle fusion and membrane remodeling). If Rabs are involved in more than one role and other components of Rab signaling also interact with more than one Rab this will further increase the complexity of the system. Elucidating the interaction of Rabs and regulation of vesicle trafficking by other signaling pathways will be a key area of research in the future.More...
Communication at the synapse involves the release of glutama......
Communication at the synapse involves the release of glutamate from the presynaptic neuron and its binding to glutamate receptors on the postsynaptic cell to generate a series of events that lead to propagation of the synaptic transmission. This process begins with the formation of synaptic vesicles in the presynaptic neuron, proceeds to the loading of glutamate into the vesicles, and concludes with the release of glutamate into the synaptic cleft. The glutamate life cycle in the neuron begins with the loading of the nascent synaptic vesicles with cytosolic glutamate with the help the transporter protein, VGLUT1, located in the synaptic vesicular membrane. Glutamate loaded vesicles are formed in the cytoplasm and then transported to a site close to the plasma membrane where the vesicle is docked with the help of several proteins. One of the key players in the docking process in Munc 18, which interacts with syntaxin (in the plasma membrane), MINT (Munc18 interacting molecule), and DOC2. These interactions along with the secondary interactions are needed for docking the synaptic vesicle to the plasma membrane. The docked synaptic vesicle is not ready for release until it undergoes molecular changes to prime it for fusion with the plasma membrane. Munc13 is one of the main players in the priming process. Munc 13 interacts with RIM (Rab3A interacting molecule) located in the synaptic vesicle. Munc 13 also interacts with DOC2. The precise molecular mechanisms of the interactions that result in docking versus priming are not clear and the docking and priming process have been combined in this annotation of this pathway. Once primed the synaptic vesicle is ready for release. Synaptic transmission involves an action potential that is generated in the presynaptic cell which induces the opening of voltage gated Ca2+ channels (VGCC) located in the plasma membrane of the presynaptic neuron. Typically N, P/Q and R type of VGCCs are involved in the neurotransmitter release. Ca2+ influx through these channels results in the rise of intracellular Ca2+ concentration. In the microdomain of glutamatergic synapses, the Ca2+ concentration could rise between 10-25 micro molar. Synaptotagmin, a Ca2+-binding protein located in the synaptic vesicular membrane, responds to the rise in the Ca2+ levels in the microdomain and induces a synaptic vesicle membrane curvature that favors vesicle fusion. Fusion of the synaptic vesicle with the plasma membrane is characterized by the formation of a trimeric trans-SNARE complex that involves VAMP2 from the synaptic vesicle membrane, and syntaxin and SNAP-25 from plasma membrane. Vesicle fusion incorporates the synaptic vesicle membrane into the plasma membrane, releasing the vesicle contents (glutamate) into the synaptic cleft. Postfusion the synaptic vesicle membrane proteins (VAMP2, Rab3A, VGLUT1, and synaptotagmin) are also found in the plasma membrane.More...
Neurotransmitter is stored in the synaptic vesicle in the pr......
Neurotransmitter is stored in the synaptic vesicle in the pre-synaptic terminal prior to its release in the synaptic cleft upon depolarization of the pre-synaptic membrane. The release of the neurotransmitter is a multi-step process that is controlled by electrical signals passing through the axons in form of action potential. Neurotransmitters include glutamate, acetylcholine, nor-epinephrine, dopamine and seratonin. Each of the neurotransmitter cycle is independently described.More...
Chemical synapses are specialized junctions that are used fo......
Chemical synapses are specialized junctions that are used for communication between neurons, neurons and muscle or gland cells. The synapse involves a pre-synaptic neuron and a post-synaptic neuron, muscle cell or glad cell. The pre and the post-synaptic cell are separated by a gap of 20nm called the synaptic cleft. The signals pass in a unidirection from pre-synaptic to post-synaptic. The pre-synaptic neuron communicates via the release of neurotransmitter which bind the receptors on the post-synaptic cell.More...
Serotonin is synthesized in the serotonergic neurons in the ......
Serotonin is synthesized in the serotonergic neurons in the central nervous system and the enterochrommaffin cells of the gastroinetstinal system. Serotonin is loaded into the clathrin sculpted monoamine transport vesicles. The vesicles are docked, primed and release after the change in the membrane potential that activates voltage gated calcium channels and the reponse by several proetins to the changes in intracellular Ca2+ increase leads to fusion of the vesicle and release of serotonin into the synapse.More...
Acetylcholine neurotransmitter release cycle involves synthe......
Acetylcholine neurotransmitter release cycle involves syntheis of choline, loading of clathrin scultpted synaptic vesicles, docking and priming of the acetyl choline loaded synaptic vesicles and then release of acetylcholine. This cycle occurs in neurons of central nervous system (CNS), peripheral, autonomic and somatic nervous system. In the CNS, the acetylcholine is released by the presynaptic neurons into the synaptic cleft where the released acetylcholine is accessible to acetylcholine receptors located on the postsynaptic neurons.More...
Noradrenalin release cycle consists of reacidification of th......
Noradrenalin release cycle consists of reacidification of the empty clathrin sculpted monoamine transport vesicle, loading of dopamine into reacidified clathrin coated monamine transport vesicle, conversion of dopamine into Noradrenalin, docking and priming of the noradrenalin synaptic veiscle and then release of noradrenalin synaptic vesicle. In the peripheral nervous system in the peripheral nervous system noradrenalin is stored in large and small dense vesicles and is realesed from large vesicles.More...
Dopamine neurotransmitter cycle occurs in dopaminergic neuro......
Dopamine neurotransmitter cycle occurs in dopaminergic neurons. Dopamine is synthesized and loaded into the clathrin sculpted monoamine transport vesicles. The vesicles are docked, primed and fused with the plasmamembrane in the synapse to release dopamine into the synaptic cleft.More...
RAB3A related interactors from protein-protein interaction data in HPRD (count: 16)