Rab proteins are essential for eukaryotic protein transport, and especially for membrane trafficking. They play a crucial role in regulation of vesicle formation, fusion, and endocytic and expocytic transport. To regulate activation and function, they interact with Rab-associated proteins. In addition, Rabs have been implicated in the docking of lipid bilayer vesicles.
The Rab family is made up of at most 60 different proteins. Some of these proteins have been preserved over time while others are more specific. These proteins are responsible for membrane trafficking and have a common GTPase activity. They are currently known to bind and activate Guanine Diphosphate (GDP), which acts as a precursor for guanine Nucleotide(GTP) hydrolysis. The active forms of Rabs are preferentially GTP-bound. Some Rab proteins, however, can be switched to GDP-bound status. GTP-bound form also has greater 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 can be found in synapses and neurons, while the Rab8 protein is somatodendritic. Some Rabs play a role in transporting cholesterol and sphingolipids. Other Rabs are associated with the cytoskeleton, membrane fusion, and the synthesis of cytosolic GTP.
The Ras superfamily's largest branch is the Rabs. They bind and activate Guanine Diphosphate and regulate vesicle creation, fusion, and endocytic transportation. Some Rabs are more specialized than others in cellular processes. Others are essential for eukaryotic existence. They are also involved in many human diseases. This review will examine recent discoveries in understanding the pathogenesis as well as the etiology behind Rab-related disease. Future studies will investigate the role of Rab family members in different cell-types.
Rabs are very dynamic in their mobility and can be involved in many pathways. In fact, their ability to interact with other Rab-associated proteins is crucial to their function. In addition to regulating the movement of vesicles, Rabs may also be responsible for docking and fusion of lipid bilayer vesicles. There are also several accessory Rab proteins, such as GDI and GEF. These proteins promote Rab GTPase activity. They aid Rabs to transition between GTP bound and GDP states.
The trafficking of vesicles is dependent on Rabs, so defects in their function may lead to various multifactorial conditions. A lack of Rab27a has been linked to hemophagic disorder, pigment anomalies, and Xlinked-non-specific mental retardation. A lack of Rab27a can also lead to neurotransmitter dysfunction, eye defects, and impaired immune function. Moreover, inherited disorders of vesicle trafficking are increasing due to defects in the Rab cycle. Common pathogenic mechanisms could be identified and improved diagnostics. These studies may lead to the development 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.