Rabaptin
Encyclopedia
Rabaptin is a key protein involved in regeneration
of injured axons.
Regeneration of injured axon
s at neuromuscular junction
s is regulated by extra-cellular protein factors that promote neurite
outgrowth. A novel neurite outgrowth factor from chick denervated skeletal muscle
has been cloned and characterised. The protein, termed neurocrescin (rabaptin), has been shown to be secreted in an activity-dependent fashion.
Rabaptin is a 100kDa coiled-coil protein that interacts with the GTP form of the small GTPase
Rab5 (see RAB5A
, RAB5B
, RAB5C
) a potent regulator of endocytic transport. It is mainly cytosolic, but a fraction co-localises with Rab5 to early endosomes. Rab5 recruits rabaptin-5 to purified early endosomes in a GTP-dependent manner, demonstrating functional similarities with other members of the Ras family. Immunodepletion of rabaptin-5 from cytosol strongly inhibits Rab5-dependent early endosome membrane fusion. Thus, rabaptin-5 is a Rab effector required for membrane docking and fusion.
Rab5 contributes to early endosome fusion that works through the coordination of other effector proteins, as mentioned above. Rabaptin components may serve to control the SNARE activity which are vital in membrane fusion.
domain of RAB5A
complexed with the C-terminal domain of Rabaptin5
has been determined. The two proteins form a symmetric RAB5A-Rabaptin5 ternary complex with a parallel coiled-coil Rabaptin5 homodimer in the middle complexed with two molecules of Rabaptin5, one on each side (see figure to the right).
Regeneration (biology)
In biology, regeneration is the process of renewal, restoration, and growth that makes genomes, cells, organs, organisms, and ecosystems resilient to natural fluctuations or events that cause disturbance or damage. Every species is capable of regeneration, from bacteria to humans. At its most...
of injured axons.
Regeneration of injured axon
Axon
An axon is a long, slender projection of a nerve cell, or neuron, that conducts electrical impulses away from the neuron's cell body or soma....
s at neuromuscular junction
Neuromuscular junction
A neuromuscular junction is the synapse or junction of the axon terminal of a motor neuron with the motor end plate, the highly-excitable region of muscle fiber plasma membrane responsible for initiation of action potentials across the muscle's surface, ultimately causing the muscle to contract...
s is regulated by extra-cellular protein factors that promote neurite
Neurite
A neurite refers to any projection from the cell body of a neuron. This projection can be either an axon or a dendrite. The term is frequently used when speaking of immature or developing neurons, especially of cells in culture, because it can be difficult to tell axons from dendrites before...
outgrowth. A novel neurite outgrowth factor from chick denervated skeletal muscle
Skeletal muscle
Skeletal muscle is a form of striated muscle tissue existing under control of the somatic nervous system- i.e. it is voluntarily controlled. It is one of three major muscle types, the others being cardiac and smooth muscle...
has been cloned and characterised. The protein, termed neurocrescin (rabaptin), has been shown to be secreted in an activity-dependent fashion.
Rabaptin is a 100kDa coiled-coil protein that interacts with the GTP form of the small GTPase
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:...
Rab5 (see RAB5A
RAB5A
Ras-related protein Rab-5A is a protein that in humans is encoded by the RAB5A gene.-Interactions:RAB5A has been shown to interact with RABEP1, SDCBP, ZFYVE20 and CHML.-Further reading:...
, RAB5B
RAB5B
Ras-related protein Rab-5B is a protein that in humans is encoded by the RAB5B gene.-Further reading:...
, RAB5C
RAB5C
Ras-related protein Rab-5C is a protein that in humans is encoded by the RAB5C gene. RAB5C belongs to the Ras-related protein family.-Further reading:...
) a potent regulator of endocytic transport. It is mainly cytosolic, but a fraction co-localises with Rab5 to early endosomes. Rab5 recruits rabaptin-5 to purified early endosomes in a GTP-dependent manner, demonstrating functional similarities with other members of the Ras family. Immunodepletion of rabaptin-5 from cytosol strongly inhibits Rab5-dependent early endosome membrane fusion. Thus, rabaptin-5 is a Rab effector required for membrane docking and fusion.
Rab5 contributes to early endosome fusion that works through the coordination of other effector proteins, as mentioned above. Rabaptin components may serve to control the SNARE activity which are vital in membrane fusion.
Structure
A crystal structure of the GTPaseGTPase
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:...
domain of RAB5A
RAB5A
Ras-related protein Rab-5A is a protein that in humans is encoded by the RAB5A gene.-Interactions:RAB5A has been shown to interact with RABEP1, SDCBP, ZFYVE20 and CHML.-Further reading:...
complexed with the C-terminal domain of Rabaptin5
RABEP1
Rab GTPase-binding effector protein 1 is an enzyme that in humans is encoded by the RABEP1 gene.. It belongs to rabaptin protein family.-Interactions:RABEP1 has been shown to interact with GGA2, RAB4A, RAB5A, AP1G1 and GGA1.-Further reading:...
has been determined. The two proteins form a symmetric RAB5A-Rabaptin5 ternary complex with a parallel coiled-coil Rabaptin5 homodimer in the middle complexed with two molecules of Rabaptin5, one on each side (see figure to the right).