Exophilin: Difference between revisions

Latest revision as of 08:12, 25 June 2019

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Rat rabphilin-3A C2A domain complex with inositol triphosphate and sulfate (PDB code 4np9)

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Function

Exophilin (EXP) are Synaptotagmin-like membrane proteins which bind Ca+2 ions and phospholipids are involved in synaptic vesicle docking.

EXP-1 or rabphilin-3A is a Rab3 effector at the synapse. Rab3A is a GTP-binding protein of synaptic vesicle that regulates vesicle exocytosis^[1]. EXP-1 regulates synaptic vesicle traffic and does so at distinct stages of both the exocytotic and endocytotic pathways^[2].
EXP-2 or granuphilin is a Rab27a effector. It is involved in tethering insulin granules to the plasma membrane in regulated exocytosis^[3] by interacting with Rab27a and Syntaxin-1a^[4].
EXP-3 or melanophilin links Myosin Va and the cargo vesicles in the cells through activation of ATPase producing the motor activity^[5].

Relevance

EXP-1 is a diagnostically useful autoantigen for lymphocytic infundibulo-neurohypophysitis^[6]. Reduction of EXP-1 immunoreactivity was found in patients of Alzheimer disease^[7]. EXP-4 or synaptotagmin-like protein 2 is associated with the metastatic potential of ovarian carcinoma^[8].

Structural highlights

The C2A domain of rabphilin-3A binds the phospholipid molecule and the phosphate ions and in a groove in the calcium-binding polybasic region of the protein^[9]. The rabphilin-3A residues interactiong with inositol triphosphate are colored according to their charge (Anionic (-) / Cationic (+)). Water molecules are shown as red spheres.

3D structures of exophilin

Exophilin 3D structures

↑ Schluter OM, Schnell E, Verhage M, Tzonopoulos T, Nicoll RA, Janz R, Malenka RC, Geppert M, Sudhof TC. Rabphilin knock-out mice reveal that rabphilin is not required for rab3 function in regulating neurotransmitter release. J Neurosci. 1999 Jul 15;19(14):5834-46. PMID:10407024
↑ Burns ME, Sasaki T, Takai Y, Augustine GJ. Rabphilin-3A: a multifunctional regulator of synaptic vesicle traffic. J Gen Physiol. 1998 Feb;111(2):243-55. PMID:9450942
↑ Gomi H, Mizutani S, Kasai K, Itohara S, Izumi T. Granuphilin molecularly docks insulin granules to the fusion machinery. J Cell Biol. 2005 Oct 10;171(1):99-109. doi: 10.1083/jcb.200505179. PMID:16216924 doi:https://dx.doi.org/10.1083/jcb.200505179
↑ Torii S, Takeuchi T, Nagamatsu S, Izumi T. Rab27 effector granuphilin promotes the plasma membrane targeting of insulin granules via interaction with syntaxin 1a. J Biol Chem. 2004 May 21;279(21):22532-8. doi: 10.1074/jbc.M400600200. Epub 2004 , Mar 17. PMID:15028737 doi:https://dx.doi.org/10.1074/jbc.M400600200
↑ Li XD, Ikebe R, Ikebe M. Activation of myosin Va function by melanophilin, a specific docking partner of myosin Va. J Biol Chem. 2005 May 6;280(18):17815-22. doi: 10.1074/jbc.M413295200. Epub 2005 , Mar 9. PMID:15760894 doi:https://dx.doi.org/10.1074/jbc.M413295200
↑ Iwama S, Sugimura Y, Kiyota A, Kato T, Enomoto A, Suzuki H, Iwata N, Takeuchi S, Nakashima K, Takagi H, Izumida H, Ochiai H, Fujisawa H, Suga H, Arima H, Shimoyama Y, Takahashi M, Nishioka H, Ishikawa SE, Shimatsu A, Caturegli P, Oiso Y. Rabphilin-3A as a Targeted Autoantigen in Lymphocytic Infundibulo-neurohypophysitis. J Clin Endocrinol Metab. 2015 Jul;100(7):E946-54. doi: 10.1210/jc.2014-4209. Epub, 2015 Apr 28. PMID:25919460 doi:https://dx.doi.org/10.1210/jc.2014-4209
↑ Tan MG, Lee C, Lee JH, Francis PT, Williams RJ, Ramirez MJ, Chen CP, Wong PT, Lai MK. Decreased rabphilin 3A immunoreactivity in Alzheimer's disease is associated with Abeta burden. Neurochem Int. 2014 Jan;64:29-36. doi: 10.1016/j.neuint.2013.10.013. Epub 2013, Nov 5. PMID:24200817 doi:https://dx.doi.org/10.1016/j.neuint.2013.10.013
↑ Sung HY, Han J, Ju W, Ahn JH. Synaptotagmin-like protein 2 gene promotes the metastatic potential in ovarian cancer. Oncol Rep. 2016 Jul;36(1):535-41. doi: 10.3892/or.2016.4835. Epub 2016 May 24. PMID:27220283 doi:https://dx.doi.org/10.3892/or.2016.4835
↑ Guillen J, Ferrer-Orta C, Buxaderas M, Perez-Sanchez D, Guerrero-Valero M, Luengo-Gil G, Pous J, Guerra P, Gomez-Fernandez JC, Verdaguer N, Corbalan-Garcia S. Structural insights into the Ca2+ and PI(4,5)P2 binding modes of the C2 domains of rabphilin 3A and synaptotagmin 1. Proc Natl Acad Sci U S A. 2013 Dec 17;110(51):20503-8. doi:, 10.1073/pnas.1316179110. Epub 2013 Dec 3. PMID:24302762 doi:https://dx.doi.org/10.1073/pnas.1316179110

References

Proteopedia Page Contributors and Editors (what is this?)

Michal Harel, Alexander Berchansky

[1] Schluter OM, Schnell E, Verhage M, Tzonopoulos T, Nicoll RA, Janz R, Malenka RC, Geppert M, Sudhof TC. Rabphilin knock-out mice reveal that rabphilin is not required for rab3 function in regulating neurotransmitter release. J Neurosci. 1999 Jul 15;19(14):5834-46. PMID:10407024

[2] Burns ME, Sasaki T, Takai Y, Augustine GJ. Rabphilin-3A: a multifunctional regulator of synaptic vesicle traffic. J Gen Physiol. 1998 Feb;111(2):243-55. PMID:9450942

[3] Gomi H, Mizutani S, Kasai K, Itohara S, Izumi T. Granuphilin molecularly docks insulin granules to the fusion machinery. J Cell Biol. 2005 Oct 10;171(1):99-109. doi: 10.1083/jcb.200505179. PMID:16216924 doi:https://dx.doi.org/10.1083/jcb.200505179

[4] Torii S, Takeuchi T, Nagamatsu S, Izumi T. Rab27 effector granuphilin promotes the plasma membrane targeting of insulin granules via interaction with syntaxin 1a. J Biol Chem. 2004 May 21;279(21):22532-8. doi: 10.1074/jbc.M400600200. Epub 2004 , Mar 17. PMID:15028737 doi:https://dx.doi.org/10.1074/jbc.M400600200

[5] Li XD, Ikebe R, Ikebe M. Activation of myosin Va function by melanophilin, a specific docking partner of myosin Va. J Biol Chem. 2005 May 6;280(18):17815-22. doi: 10.1074/jbc.M413295200. Epub 2005 , Mar 9. PMID:15760894 doi:https://dx.doi.org/10.1074/jbc.M413295200

[6] Iwama S, Sugimura Y, Kiyota A, Kato T, Enomoto A, Suzuki H, Iwata N, Takeuchi S, Nakashima K, Takagi H, Izumida H, Ochiai H, Fujisawa H, Suga H, Arima H, Shimoyama Y, Takahashi M, Nishioka H, Ishikawa SE, Shimatsu A, Caturegli P, Oiso Y. Rabphilin-3A as a Targeted Autoantigen in Lymphocytic Infundibulo-neurohypophysitis. J Clin Endocrinol Metab. 2015 Jul;100(7):E946-54. doi: 10.1210/jc.2014-4209. Epub, 2015 Apr 28. PMID:25919460 doi:https://dx.doi.org/10.1210/jc.2014-4209

[7] Tan MG, Lee C, Lee JH, Francis PT, Williams RJ, Ramirez MJ, Chen CP, Wong PT, Lai MK. Decreased rabphilin 3A immunoreactivity in Alzheimer's disease is associated with Abeta burden. Neurochem Int. 2014 Jan;64:29-36. doi: 10.1016/j.neuint.2013.10.013. Epub 2013, Nov 5. PMID:24200817 doi:https://dx.doi.org/10.1016/j.neuint.2013.10.013

[8] Sung HY, Han J, Ju W, Ahn JH. Synaptotagmin-like protein 2 gene promotes the metastatic potential in ovarian cancer. Oncol Rep. 2016 Jul;36(1):535-41. doi: 10.3892/or.2016.4835. Epub 2016 May 24. PMID:27220283 doi:https://dx.doi.org/10.3892/or.2016.4835

[9] Guillen J, Ferrer-Orta C, Buxaderas M, Perez-Sanchez D, Guerrero-Valero M, Luengo-Gil G, Pous J, Guerra P, Gomez-Fernandez JC, Verdaguer N, Corbalan-Garcia S. Structural insights into the Ca2+ and PI(4,5)P2 binding modes of the C2 domains of rabphilin 3A and synaptotagmin 1. Proc Natl Acad Sci U S A. 2013 Dec 17;110(51):20503-8. doi:, 10.1073/pnas.1316179110. Epub 2013 Dec 3. PMID:24302762 doi:https://dx.doi.org/10.1073/pnas.1316179110

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@@ Line 5: / Line 5: @@
 '''Exophilin''' (EXP) are [[Synaptotagmin]]-like membrane proteins which bind Ca+2 ions and phospholipids are involved in synaptic vesicle docking.
-* EXP-1 or '''rabphilin-3A''' is a Rab3 effector at the synapse.  Rab3A is a GTP-binding protein of synaptic vesicle that regulates vesicle exocytosis<ref>PMID:10407024</ref>.  EXP-1 regulates synaptic vesicle traffic and does so at distinct stages of both the exocytotic and endocytotic pathways<ref>PMID:9450942</ref>.<br />
+* '''EXP-1''' or '''rabphilin-3A''' is a Rab3 effector at the synapse.  Rab3A is a GTP-binding protein of synaptic vesicle that regulates vesicle exocytosis<ref>PMID:10407024</ref>.  EXP-1 regulates synaptic vesicle traffic and does so at distinct stages of both the exocytotic and endocytotic pathways<ref>PMID:9450942</ref>.<br />
-* EXP-2 or '''granuphilin''' is a Rab27a effector.  It is involved in tethering insulin granules to the plasma membrane in regulated exocytosis<ref>PMID:16216924</ref> by interacting with Rab27a and [[Syntaxin]]-1a<ref>PMID:15028737</ref>.<br />
+* '''EXP-2''' or '''granuphilin''' is a Rab27a effector.  It is involved in tethering insulin granules to the plasma membrane in regulated exocytosis<ref>PMID:16216924</ref> by interacting with Rab27a and [[Syntaxin]]-1a<ref>PMID:15028737</ref>.<br />
-* EXP-3 or '''melanophilin''' links [[Myosin]] Va and the cargo vesicles in the cells through activation of ATPase producing the motor activity<ref>PMID:15760894</ref>.<br />
+* '''EXP-3''' or '''melanophilin''' links [[Myosin]] Va and the cargo vesicles in the cells through activation of ATPase producing the motor activity<ref>PMID:15760894</ref>.<br />
 == Relevance ==
@@ Line 15: / Line 15: @@
 == Structural highlights ==
-The <scene name='80/802738/Cv/3'>C2A domain of rabphilin-3A binds the phospholipid molecule</scene> and the phosphate ions and in a groove in the calcium-binding polybasic region of the protein<ref>PMID:24302762</ref>. The rabphilin-3A residues interactiong with inositol triphosphate are colored according to their charge.  Water molecules are shown as red spheres.
+The <scene name='80/802738/Cv/3'>C2A domain of rabphilin-3A binds the phospholipid molecule</scene> and the phosphate ions and <scene name='80/802738/Cv/6'>in a groove</scene> in the calcium-binding polybasic region of the protein<ref>PMID:24302762</ref>. The rabphilin-3A residues interactiong with inositol triphosphate are colored according to their charge ({{Template:ColorKey_Charge_Anionic}} / {{Template:ColorKey_Charge_Cationic}}). Water molecules are shown as red spheres.
-</StructureSection>
 ==3D structures of exophilin==
+[[Exophilin 3D structures]]
-Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}
+</StructureSection>
-{{#tree:id=OrganizedByTopic|openlevels=0|
-*Exophilin-1 or rabphilin-3A
-**[[2chd]], [[4lt7]] – rEXP C2A domain - rat<br />
-**[[2cm6]], [[2cm5]] – rEXP C2B domain <br />
-**[[4np9]], [[4ns0]] – rEXP C2A domain + inositol phosphate derivative<br />
-**[[5lo8]] – rEXP C2B domain + inositol phosphate derivative<br />
-**[[5low]], [[5lob]] – rEXP C2B domain + SNAP25<br />
-*Exophilin-2 or synaptostagmin-like protein 4 or granuphilin
-**[[2csz]], [[5x6t]] – hEXP RING domain - NMR<br />
-**[[3fdw]] – hEXP C2 domain <br />
-*Exophilin-3 or synaptotagmin-like protein 2A or melanophilin
-**[[2zet]] – mEXP SLP homology domain + RAB-27A - mouse<br />
-**[[4kp3]] – mEXP SLP globular tail domain + myosin-VA + RILPL2 <br />
-**[[4lx2]] – mEXP SLP globular tail domain + myosin-VA <br />
-*Exophilin-4 or synaptotagmin-like protein 2
-**[[3bc1]] – hEXP Rab-binding domain + Rab27A<br />
-}}
 == References ==
 <references/>
 [[Category:Topic Page]]

Exophilin: Difference between revisions

Latest revision as of 08:12, 25 June 2019

Contents

Function

Relevance

Structural highlights

3D structures of exophilin

References

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