User:Myriam Deshaies/Sandbox 1
From Proteopedia
| Line 3: | Line 3: | ||
The Rab family of proteins is one of the Ras family of monomeric G proteins. There are approximately 70 types of known Rabs in humans. Rab GTPases are involved in the regulation of vesicular traffic in eukaryotic cells, among which vesicle formation, vesicle movement along actin and tubulin network and membrane fusion. Rab proteins are bound at the surface of the membrane by a lipid group covalently linked to an amino acid. As Rabs are GTPases, they have two conformations. The inactive form is bound to GDP and the active one is linked to GTP. Rab escort proteins only bound Rab-GDP and Rab effectors only bound Rab-GTP. Rabs work thanks to Rab effectors. | The Rab family of proteins is one of the Ras family of monomeric G proteins. There are approximately 70 types of known Rabs in humans. Rab GTPases are involved in the regulation of vesicular traffic in eukaryotic cells, among which vesicle formation, vesicle movement along actin and tubulin network and membrane fusion. Rab proteins are bound at the surface of the membrane by a lipid group covalently linked to an amino acid. As Rabs are GTPases, they have two conformations. The inactive form is bound to GDP and the active one is linked to GTP. Rab escort proteins only bound Rab-GDP and Rab effectors only bound Rab-GTP. Rabs work thanks to Rab effectors. | ||
| - | Rab27A and Rab27B are isoforms (72% of identity) and use several specific effector proteins, among which the Exophilin3/Melanophilin/Slac2-a, to regulate the exocytosis of secretory granule cells. Two groups of Rab27 effectors can be made, depending on their interactions specificities. The first one is composed of Melanophilin, Exophilin4, Exophilin5 and Exophilin6, which are specific effectors for Rab27. The other group consists of Rabphilin-3a, Granuphilin-a and JFC1, which are also effectors for Rab3 and Rab8 for instance. Rab27A/B proteins are not only involved in the transport of lysosome-related organelles regulation and may regulate more types | + | Rab27A and Rab27B are isoforms (72% of identity) and use several specific effector proteins, among which the Exophilin3/Melanophilin/Slac2-a, to regulate the exocytosis of secretory granule cells. Two groups of Rab27 effectors can be made, depending on their interactions specificities. The first one is composed of Melanophilin, Exophilin4, Exophilin5 and Exophilin6, which are specific effectors for Rab27. The other group consists of Rabphilin-3a, Granuphilin-a and JFC1, which are also effectors for Rab3 and Rab8 for instance. Rab27A/B proteins are not only involved in the transport of lysosome-related organelles regulation and may regulate more types of granule exocytosis mechanisms, like endocrine. |
| - | Mutations of Rab27A cause human type II Griscelli syndrome (hypopigmentation and immunodeficiency disorder) because of a defect in melanosome transport in melanocytes. Rab27A orchestrates the transport of melanosomes by recruitment of the actin motor, myosin Va, onto melanosomes. Rab27A links the melanosome and then recruits melanophilin, which finally bounds | + | Mutations of Rab27A cause human type II Griscelli syndrome (hypopigmentation and immunodeficiency disorder) because of a defect in melanosome transport in melanocytes. Rab27A orchestrates the transport of melanosomes by recruitment of the actin motor, myosin Va, onto melanosomes. Rab27A links the melanosome and then recruits melanophilin, which finally bounds myosin-Va. Because Rab27A and Rab27B are isoforms and the effects of Rab27A mutations, it is interested to study Rab27B. |
| Line 13: | Line 13: | ||
===Rab27B=== | ===Rab27B=== | ||
| - | At the moment, no Rab27B mutation is known to cause human disease or animal strain. | + | At the moment, no Rab27B mutation is known to cause human disease or animal strain. But Rab27B is known to localise on pituitary endocrines granules, dense and α-granules in platelets and megakaryocytes, urothelial fusiform vesicles and parotid and pancreatic acinar granules. Rab27B is largely expressed in canonical secretory cells, neurons and cells involved in surface protection and mechanical extension. Rab27B regulates a secretory granule exocytosis step in parotid acinar cells. It has several Rab27B effector proteins. For example, the interaction of Rab27B with Slac2-c/MyRIP is very important for amylase release. Slac2-c is a myosin Va/VIIa and actin binding protein and may work for retinal melanosome transport in melanocytes regulation. Rab27B exists on amylase containing secretory granules in the rat parotid gland. That is why the Rab27B-Slac2-c complex is important to release amylase. Rab27B is the first Rab protein known to contribute in the exocytosis of secretory granules in parotid acinar cells. |
===Exophilin3/Slac2-a/Melanophilin=== | ===Exophilin3/Slac2-a/Melanophilin=== | ||
| - | As written before, melanophilin is a Rab27A/B effector. Slac2-a acts in the regulation of melanosome transport in mammalian skin melanocytes by binding melanosome-bound Rab27A and myosin Va, an actin-based motor protein | + | As written before, melanophilin is a Rab27A/B effector. Slac2-a acts in the regulation of melanosome transport in mammalian skin melanocytes by binding melanosome-bound Rab27A and myosin Va, an actin-based motor protein. |
Although Slac2-a directly interacts with Rab27A and myosin Va via its N-terminal region (amino acids 1 to 146) and the middle region (amino acids 241 to 405), respectively, the functional importance of the putative actin-binding domain of the Slac2-a C terminus (amino acids 401 to 590) in melanosome transport has never been elucidated. | Although Slac2-a directly interacts with Rab27A and myosin Va via its N-terminal region (amino acids 1 to 146) and the middle region (amino acids 241 to 405), respectively, the functional importance of the putative actin-binding domain of the Slac2-a C terminus (amino acids 401 to 590) in melanosome transport has never been elucidated. | ||
Revision as of 14:25, 6 January 2013
Contents |
Introduction
The Rab family of proteins is one of the Ras family of monomeric G proteins. There are approximately 70 types of known Rabs in humans. Rab GTPases are involved in the regulation of vesicular traffic in eukaryotic cells, among which vesicle formation, vesicle movement along actin and tubulin network and membrane fusion. Rab proteins are bound at the surface of the membrane by a lipid group covalently linked to an amino acid. As Rabs are GTPases, they have two conformations. The inactive form is bound to GDP and the active one is linked to GTP. Rab escort proteins only bound Rab-GDP and Rab effectors only bound Rab-GTP. Rabs work thanks to Rab effectors.
Rab27A and Rab27B are isoforms (72% of identity) and use several specific effector proteins, among which the Exophilin3/Melanophilin/Slac2-a, to regulate the exocytosis of secretory granule cells. Two groups of Rab27 effectors can be made, depending on their interactions specificities. The first one is composed of Melanophilin, Exophilin4, Exophilin5 and Exophilin6, which are specific effectors for Rab27. The other group consists of Rabphilin-3a, Granuphilin-a and JFC1, which are also effectors for Rab3 and Rab8 for instance. Rab27A/B proteins are not only involved in the transport of lysosome-related organelles regulation and may regulate more types of granule exocytosis mechanisms, like endocrine.
Mutations of Rab27A cause human type II Griscelli syndrome (hypopigmentation and immunodeficiency disorder) because of a defect in melanosome transport in melanocytes. Rab27A orchestrates the transport of melanosomes by recruitment of the actin motor, myosin Va, onto melanosomes. Rab27A links the melanosome and then recruits melanophilin, which finally bounds myosin-Va. Because Rab27A and Rab27B are isoforms and the effects of Rab27A mutations, it is interested to study Rab27B.
Biological functions
Rab27B
At the moment, no Rab27B mutation is known to cause human disease or animal strain. But Rab27B is known to localise on pituitary endocrines granules, dense and α-granules in platelets and megakaryocytes, urothelial fusiform vesicles and parotid and pancreatic acinar granules. Rab27B is largely expressed in canonical secretory cells, neurons and cells involved in surface protection and mechanical extension. Rab27B regulates a secretory granule exocytosis step in parotid acinar cells. It has several Rab27B effector proteins. For example, the interaction of Rab27B with Slac2-c/MyRIP is very important for amylase release. Slac2-c is a myosin Va/VIIa and actin binding protein and may work for retinal melanosome transport in melanocytes regulation. Rab27B exists on amylase containing secretory granules in the rat parotid gland. That is why the Rab27B-Slac2-c complex is important to release amylase. Rab27B is the first Rab protein known to contribute in the exocytosis of secretory granules in parotid acinar cells.
Exophilin3/Slac2-a/Melanophilin
As written before, melanophilin is a Rab27A/B effector. Slac2-a acts in the regulation of melanosome transport in mammalian skin melanocytes by binding melanosome-bound Rab27A and myosin Va, an actin-based motor protein. Although Slac2-a directly interacts with Rab27A and myosin Va via its N-terminal region (amino acids 1 to 146) and the middle region (amino acids 241 to 405), respectively, the functional importance of the putative actin-binding domain of the Slac2-a C terminus (amino acids 401 to 590) in melanosome transport has never been elucidated.
Rab27B complexed with the Slp homology domain of Slac2-a
Little is known about the interactions between Rab27B and melanophilin. The Rab27B/Slac2-a complex has several intermolecular hydrogen bonds and electrostatic interactions. It may be used for drugs development for the Griscelli syndrome.
