The transport of proteins is a key function of Rab proteins in eukaryotic cell trafficking. They are involved in regulating vesicle growth, fusion, and endocytic/exocytic transport. They interact with Rab proteins to regulate their activation, function, and also interact with them. Rabs are implicated in docking of lipid bilayer vessels.
The Rab family is composed of at least 60 different proteins. Some proteins are conserved over time, while others have evolved for more specific functions. These proteins share a common GTPase activity, and are responsible to membrane trafficking. They are known to bind, activate and inhibit guanine phosphate. This is the precursor for guanine nitide (GTP), hydrolysis. GTP-bound Rabs are the most active forms. However, some Rab proteins are able to switch to GDP-bound state. GTP-bound forms also have enhanced affinity for effectors.
The Rab family is home to a wide range of small guanosinetriphosphatases. Most of the Rabs are expressed in all cell types, but a few are specialized in particular pathways. The Rab3A protein is found in synapses as well as neurons. While the Rab8 protein is somatodendritic, it can be found in neurons. Some Rabs may be involved in the transport sphingolipids or cholesterol. Others are involved in the cytoskeleton and membrane fusion as well as the synthesis of cytosolic TTP.
The Ras superfamily's largest branch is the Rabs. They bind and activate guanine diphosphate and are involved in the regulation of vesicle formation, fusion and endocytic transport. Some Rabs specialize in specific cellular processes while others are critical for eukaryotic life. They are also involved in many human diseases. This review will concentrate on recent advancements in understanding the etiology, pathogenesis, and prevention of Rab-related disorders. Future research will examine the role of Rab members in different cell-types.
Rabs have a high degree of mobility and are involved in many pathways. In fact, Rabs are essential for their function because they can interact with other Rab protein-associated proteins. In addition to regulating the movement of vesicles, Rabs may also be responsible for docking and fusion of lipid bilayer vesicles. GEF and GDI are two additional Rab proteins. These proteins promote Rab GTPase activity. These proteins also aid Rabs in balancing between GTP-bound state and GDP.
The trafficking of vesicles is dependent on Rabs, so defects in their function may lead to various multifactorial conditions. Lack of Rab27a can lead to hemophagic syndrome, pigment abnormalities, and X-linked, non-specific mental retardation. Deficient Rabs are also thought to cause neurotransmitter dysregulation and eye defects as well as impaired immune function. The Rab cycle defect is also causing an increase in inherited disorders of Vesicle Trafficking. These diseases can be diagnosed more easily if common pathogenic mechanisms are discovered. These studies could also lead the development and testing of therapeutic agents.
Rabs also play a crucial role in brain development. Rab3A can be found in neurons, platelets and is needed for calcium-dependent neurotransmitters to be released. The trafficking of melanosomes is also dependent on the Rab27a/Mlph/MyoVa combination.