| Structural highlights
Function
[PI4KB_HUMAN] Phosphorylates phosphatidylinositol (PI) in the first committed step in the production of the second messenger inositol-1,4,5,-trisphosphate (PIP). May regulate Golgi disintegration/reorganization during mitosis, possibly via its phosphorylation. Involved in Golgi-to-plasma membrane trafficking (By similarity).[1] [2] [3] [RB11A_HUMAN] The small GTPases Rab are key regulators of intracellular membrane trafficking, from the formation of transport vesicles to their fusion with membranes. Rabs cycle between an inactive GDP-bound form and an active GTP-bound form that is able to recruit to membranes different set of downstream effectors directly responsible for vesicle formation, movement, tethering and fusion. That Rab regulates endocytic recycling. Acts as a major regulator of membrane delivery during cytokinesis. Together with MYO5B and RAB8A participates in epithelial cell polarization. Together with RAB3IP, RAB8A, the exocyst complex, PARD3, PRKCI, ANXA2, CDC42 and DNMBP promotes transcytosis of PODXL to the apical membrane initiation sites (AMIS), apical surface formation and lumenogenesis. Together with MYO5B participates in CFTR trafficking to the plasma membrane and TF (Transferrin) recycling in nonpolarized cells. Required in a complex with MYO5B and RAB11FIP2 for the transport of NPC1L1 to the plasma membrane. Participates in the sorting and basolateral transport of CDH1 from the Golgi apparatus to the plasma membrane. Regulates the recycling of FCGRT (receptor of Fc region of monomeric Ig G) to basolateral membranes. May also play a role in melanosome transport and release from melanocytes.[4] [5] [6] [7] [8] [9]
Publication Abstract from PubMed
Phosphatidylinositol 4-kinases (PI4Ks) and small guanosine triphosphatases (GTPases) are essential for processes that require expansion and remodeling of phosphatidylinositol 4-phosphate (PI4P)-containing membranes, including cytokinesis, intracellular development of malarial pathogens, and replication of a wide range of RNA viruses. However, the structural basis for coordination of PI4K, GTPases, and their effectors is unknown. Here, we describe structures of PI4Kbeta (PI4KIIIbeta) bound to the small GTPase Rab11a without and with the Rab11 effector protein FIP3. The Rab11-PI4KIIIbeta interface is distinct compared with known structures of Rab complexes and does not involve switch regions used by GTPase effectors. Our data provide a mechanism for how PI4KIIIbeta coordinates Rab11 and its effectors on PI4P-enriched membranes and also provide strategies for the design of specific inhibitors that could potentially target plasmodial PI4KIIIbeta to combat malaria.
Structures of PI4KIIIbeta complexes show simultaneous recruitment of Rab11 and its effectors.,Burke JE, Inglis AJ, Perisic O, Masson GR, McLaughlin SH, Rutaganira F, Shokat KM, Williams RL Science. 2014 May 30;344(6187):1035-8. doi: 10.1126/science.1253397. PMID:24876499[10]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Suzuki K, Hirano H, Okutomi K, Suzuki M, Kuga Y, Fujiwara T, Kanemoto N, Isono K, Horie M. Identification and characterization of a novel human phosphatidylinositol 4-kinase. DNA Res. 1997 Aug 31;4(4):273-80. PMID:9405935
- ↑ Godi A, Pertile P, Meyers R, Marra P, Di Tullio G, Iurisci C, Luini A, Corda D, De Matteis MA. ARF mediates recruitment of PtdIns-4-OH kinase-beta and stimulates synthesis of PtdIns(4,5)P2 on the Golgi complex. Nat Cell Biol. 1999 Sep;1(5):280-7. PMID:10559940 doi:http://dx.doi.org/10.1038/12993
- ↑ Heilmeyer LM Jr, Vereb G Jr, Vereb G, Kakuk A, Szivak I. Mammalian phosphatidylinositol 4-kinases. IUBMB Life. 2003 Feb;55(2):59-65. PMID:12749687 doi:http://dx.doi.org/10.1002/tbmb.718540873
- ↑ Wilson GM, Fielding AB, Simon GC, Yu X, Andrews PD, Hames RS, Frey AM, Peden AA, Gould GW, Prekeris R. The FIP3-Rab11 protein complex regulates recycling endosome targeting to the cleavage furrow during late cytokinesis. Mol Biol Cell. 2005 Feb;16(2):849-60. Epub 2004 Dec 15. PMID:15601896 doi:10.1091/mbc.E04-10-0927
- ↑ Lock JG, Stow JL. Rab11 in recycling endosomes regulates the sorting and basolateral transport of E-cadherin. Mol Biol Cell. 2005 Apr;16(4):1744-55. Epub 2005 Feb 2. PMID:15689490 doi:10.1091/mbc.E04-10-0867
- ↑ Swiatecka-Urban A, Talebian L, Kanno E, Moreau-Marquis S, Coutermarsh B, Hansen K, Karlson KH, Barnaby R, Cheney RE, Langford GM, Fukuda M, Stanton BA. Myosin Vb is required for trafficking of the cystic fibrosis transmembrane conductance regulator in Rab11a-specific apical recycling endosomes in polarized human airway epithelial cells. J Biol Chem. 2007 Aug 10;282(32):23725-36. Epub 2007 Apr 26. PMID:17462998 doi:10.1074/jbc.M608531200
- ↑ Chu BB, Ge L, Xie C, Zhao Y, Miao HH, Wang J, Li BL, Song BL. Requirement of myosin Vb.Rab11a.Rab11-FIP2 complex in cholesterol-regulated translocation of NPC1L1 to the cell surface. J Biol Chem. 2009 Aug 14;284(33):22481-90. doi: 10.1074/jbc.M109.034355. Epub, 2009 Jun 19. PMID:19542231 doi:10.1074/jbc.M109.034355
- ↑ Bryant DM, Datta A, Rodriguez-Fraticelli AE, Peranen J, Martin-Belmonte F, Mostov KE. A molecular network for de novo generation of the apical surface and lumen. Nat Cell Biol. 2010 Nov;12(11):1035-45. doi: 10.1038/ncb2106. Epub 2010 Oct 3. PMID:20890297 doi:10.1038/ncb2106
- ↑ Roland JT, Bryant DM, Datta A, Itzen A, Mostov KE, Goldenring JR. Rab GTPase-Myo5B complexes control membrane recycling and epithelial polarization. Proc Natl Acad Sci U S A. 2011 Feb 15;108(7):2789-94. doi:, 10.1073/pnas.1010754108. Epub 2011 Jan 31. PMID:21282656 doi:10.1073/pnas.1010754108
- ↑ Burke JE, Inglis AJ, Perisic O, Masson GR, McLaughlin SH, Rutaganira F, Shokat KM, Williams RL. Structures of PI4KIIIbeta complexes show simultaneous recruitment of Rab11 and its effectors. Science. 2014 May 30;344(6187):1035-8. doi: 10.1126/science.1253397. PMID:24876499 doi:http://dx.doi.org/10.1126/science.1253397
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