Structural highlights
Function
RAB8A_HUMAN May be involved in vesicular trafficking and neurotransmitter release. Together with RAB11A, RAB3IP, 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 and RAB11A participates in epithelial cell polarization.[1] [2]
Publication Abstract from PubMed
Rab8a is associated with the dynamic regulation of membrane protrusions in polarized cells. Rab8a is one of several Rab GTPases that are substrates of leucine-rich repeat kinase 2 (LRRK2), a serine/threonine kinase that is linked to Parkinson's disease. Rab8a is phosphorylated at T72 (pT72) in its switch 2 helix and recruits the phospho-specific effector RILPL2, which subsequently regulates ciliogenesis. Here, we report the crystal structure of phospho-Rab8a (pRab8a) in complex with the RH2 (RILP homology) domain of RILPL2. The complex is a heterotetramer with RILPL2 forming a central alpha-helical dimer that bridges two pRab8a molecules. The N termini of the alpha helices cross over, forming an X-shaped cap (X-cap) that orients Arg residues from RILPL2 toward pT72. X-cap residues critical for pRab8a binding are conserved in JIP3 and JIP4, which also interact with LRRK2-phosphorylated Rab10. We propose a general mode of recognition for phosphorylated Rab GTPases by this family of phospho-specific effectors.
Structural Basis for Rab8a Recruitment of RILPL2 via LRRK2 Phosphorylation of Switch 2.,Waschbusch D, Purlyte E, Pal P, McGrath E, Alessi DR, Khan AR Structure. 2020 Feb 1. pii: S0969-2126(20)30005-8. doi:, 10.1016/j.str.2020.01.005. PMID:32017888[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ 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
- ↑ Waschbusch D, Purlyte E, Pal P, McGrath E, Alessi DR, Khan AR. Structural Basis for Rab8a Recruitment of RILPL2 via LRRK2 Phosphorylation of Switch 2. Structure. 2020 Feb 1. pii: S0969-2126(20)30005-8. doi:, 10.1016/j.str.2020.01.005. PMID:32017888 doi:http://dx.doi.org/10.1016/j.str.2020.01.005
