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Rabaptin is a key protein involved in
regeneration Regeneration may refer to: Science and technology * Regeneration (biology), the ability to recreate lost or damaged cells, tissues, organs and limbs * Regeneration (ecology), the ability of ecosystems to regenerate biomass, using photosynthesis ...
of injured
axons An axon (from Greek ἄξων ''áxōn'', axis), or nerve fiber (or nerve fibre: see spelling differences), is a long, slender projection of a nerve cell, or neuron, in vertebrates, that typically conducts electrical impulses known as action po ...
. Regeneration of injured
axon An axon (from Greek ἄξων ''áxōn'', axis), or nerve fiber (or nerve fibre: see spelling differences), is a long, slender projection of a nerve cell, or neuron, in vertebrates, that typically conducts electrical impulses known as action ...
s at
neuromuscular junction A neuromuscular junction (or myoneural junction) is a chemical synapse between a motor neuron and a muscle fiber. It allows the motor neuron to transmit a signal to the muscle fiber, causing muscle contraction. Muscles require innervation ...
s is regulated by extra-cellular protein factors that promote
neurite A neurite or neuronal process 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 cultur ...
outgrowth. A novel neurite outgrowth factor from chick denervated
skeletal muscle Skeletal muscles (commonly referred to as muscles) are organs of the vertebrate muscular system and typically are attached by tendons to bones of a skeleton. The muscle cells of skeletal muscles are much longer than in the other types of m ...
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 GTPases are a large family of hydrolase enzymes that bind to the nucleotide guanosine triphosphate (GTP) and hydrolyze it to guanosine diphosphate (GDP). The GTP binding and hydrolysis takes place in the highly conserved P-loop "G domain", a ...
Rab5 (see
RAB5A Ras-related protein Rab-5A is a protein that in humans is encoded by the ''RAB5A'' gene. Function RAB5A localizes to early endosomes where it is involved in the recruitment of RAB7A and the maturation of these compartments to late endosomes. I ...
, RAB5B,
RAB5C Ras-related protein Rab-5C is a protein that in humans is encoded by the ''RAB5C'' gene In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' ...
) a potent regulator of endocytic transport. It is mainly cytosolic, but a fraction co-localises with Rab5 to early
endosomes Endosomes are a collection of intracellular sorting organelles in eukaryotic cells. They are parts of endocytic membrane transport pathway originating from the trans Golgi network. Molecules or ligands internalized from the plasma membrane ...
. 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 A membrane is a selective barrier; it allows some things to pass through but stops others. Such things may be molecules, ions, or other small particles. Membranes can be generally classified into synthetic membranes and biological membranes. ...
. 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
GTPase GTPases are a large family of hydrolase enzymes that bind to the nucleotide guanosine triphosphate (GTP) and hydrolyze it to guanosine diphosphate (GDP). The GTP binding and hydrolysis takes place in the highly conserved P-loop "G domain", a ...
domain of
RAB5A Ras-related protein Rab-5A is a protein that in humans is encoded by the ''RAB5A'' gene. Function RAB5A localizes to early endosomes where it is involved in the recruitment of RAB7A and the maturation of these compartments to late endosomes. I ...
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).


Human proteins

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: * AP1G1, * GGA1, * GGA2 ADP-ribosylation fac ...
; RABEP2;


References

Protein domains Protein families Membrane proteins {{membrane-protein-stub