Rab27
Encyclopedia
Rab27 is a member of the Rab
Rab (G-protein)
The Rab family of proteins is a member of the Ras superfamily of monomeric G proteins. Approximately 70 types of Rabs have now been identified in humans. Rab GTPases regulate many steps of membrane traffic, including vesicle formation, vesicle movement along actin and tubulin networks, and membrane...

 subfamily of 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:...

s. Rab27 is post translationally modified by the addition of two geranylgeranyl groups
Prenylation
Prenylation, or isoprenylation, or lipidation is the addition of hydrophobic molecules to a protein. It is usually assumed that prenyl groups facilitate attachment to cell membranes, similar to lipid anchor like the GPI anchor, though direct evidence is missing...

 on the two C-terminal cysteine
Cysteine
Cysteine is an α-amino acid with the chemical formula HO2CCHCH2SH. It is a non-essential amino acid, which means that it is biosynthesized in humans. Its codons are UGU and UGC. The side chain on cysteine is thiol, which is polar and thus cysteine is usually classified as a hydrophilic amino acid...

s.

Pathology

Mutations that prevent the expression of Rab27 ('knock out' mutations) cause the hypopigmentation and immunodefficiency disorder known as type II Griscelli syndrome
Griscelli syndrome
Griscelli syndrome is a rare autosomal recessive disorder characterized by albinism with immunodeficiency, that usually causes death by early childhood.-Types:...

, while a decrease in Rab27 prenylation is thought to be involved in choroideremia
Choroideremia
Choroideremia is an X-linked recessive retinal degenerative disease that leads to the degeneration of the choriocapillaris, the retinal pigment epithelium, and the photoreceptor of the eye....

.

The symptoms of type II Griscelli syndrome
Griscelli syndrome
Griscelli syndrome is a rare autosomal recessive disorder characterized by albinism with immunodeficiency, that usually causes death by early childhood.-Types:...

 have shown that Rab27 is involved in melanosome
Melanosome
In a biological cell, a melanosome is an organelle containing melanin, the most common light-absorbing pigment found in the animal kingdom.Cells that synthesize melanins are called melanocytes, and also the retinal pigment epithelium cells, whereas cells that have merely engulfed the melanosomes...

 transport in melanocytes and in cytotoxic killing activity in cytotoxic T lymphoblasts. In melanocytes Rab27 binds the melanosome. The melanosome is transported along the microtubule
Microtubule
Microtubules are a component of the cytoskeleton. These rope-like polymers of tubulin can grow as long as 25 micrometers and are highly dynamic. The outer diameter of microtubule is about 25 nm. Microtubules are important for maintaining cell structure, providing platforms for intracellular...

. Rab27 then recruits Slac2A and myosin
Myosin
Myosins comprise a family of ATP-dependent motor proteins and are best known for their role in muscle contraction and their involvement in a wide range of other eukaryotic motility processes. They are responsible for actin-based motility. The term was originally used to describe a group of similar...

 Va, these enzymes are essential for the transfer of the melanosomes from the microtubules to actin
Actin
Actin is a globular, roughly 42-kDa moonlighting protein found in all eukaryotic cells where it may be present at concentrations of over 100 μM. It is also one of the most highly-conserved proteins, differing by no more than 20% in species as diverse as algae and humans...

 filaments. The melanosomes can now continue on their path towards the cell periphery. If either Rab27, Slac2A or myosin Va are absent then the melansomes remain in the perinuclear region of the cell. This disruption in pigmentation results in the hypopigmentation seen in the silvery hair colour of patients with Griscelli syndrome
Griscelli syndrome
Griscelli syndrome is a rare autosomal recessive disorder characterized by albinism with immunodeficiency, that usually causes death by early childhood.-Types:...

.
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