Ciliary membrane proteins traffic through the Golgi via a Rabep1/GGA1/Arl3-dependent mechanism

作者: Hyunho Kim , Hangxue Xu , Qin Yao , Weizhe Li , Qiong Huang

DOI: 10.1038/NCOMMS6482

关键词:

摘要: Primary cilia contain specific receptors and channel proteins that sense the extracellular milieu. Defective ciliary function causes ciliopathies such as autosomal dominant polycystic kidney disease (ADPKD). However, little is known about how large transmembrane traffic to cilia. Polycystin-1 (PC1) -2 (PC2), two ADPKD gene products, are co-localize where they act control proper tubular diameter. Here we describe PC1 PC2 must interact form a complex reach trans-Golgi network (TGN) for subsequent targeting. also be proteolytically cleaved at GPS site this occur. Using yeast two-hybrid screening coupled with candidate approach, identify Rabep1/GGA1/Arl3-dependent targeting mechanism, whereby Rabep1 couples polycystin GGA1/Arl3-based trafficking module TGN. This study provides novel insights into mechanism of membrane proteins.

参考文章(70)
Lotte B. Pedersen, Joel L. Rosenbaum, Chapter Two Intraflagellar Transport (IFT) Ciliary Function in Mammalian Development. ,vol. 85, pp. 23- 61 ,(2008) , 10.1016/S0070-2153(08)00802-8
Kazushige Hanaoka, Feng Qian, Alessandra Boletta, Anil K. Bhunia, Klaus Piontek, Leonidas Tsiokas, Vikas P. Sukhatme, William B. Guggino, Gregory G. Germino, Co-assembly of polycystin-1 and -2 produces unique cation-permeable currents Nature. ,vol. 408, pp. 990- 994 ,(2000) , 10.1038/35050128
Christopher J Ward, B Peral, J Hughes, S Thomas, V Gamble, AB MacCarthy, J Sloanestanley, VJ Buckle, L Kearney, DR Higgs, PJ Ratcliffe, PC Harris, JH Roelfsema, L Spruit, JJ Saris, HG Dauwerse, DJM Peters, MH Breuning, M Nellist, PT BROOKCARTER, MM Maheshwar, I Cordeiro, H Santos, P Cabral, JR Sampson, B Janssen, ALW HESSELINGJANSSEN, AMW VANDENOUWELAND, B Eussen, S Verhoef, D Lindhout, DJJ Halley, None, The polycystic kidney disease 1 gene encodes a 14 kb transcript and lies within a duplicated region on chromosome 16 Cell. ,vol. 77, pp. 881- 894 ,(1994) , 10.1016/0092-8674(94)90137-6
Shehab A Ismail, Yong-Xiang Chen, Mandy Miertzschke, Ingrid R Vetter, Carolin Koerner, Alfred Wittinghofer, Structural basis for Arl3-specific release of myristoylated ciliary cargo from UNC119. The EMBO Journal. ,vol. 31, pp. 4085- 4094 ,(2012) , 10.1038/EMBOJ.2012.257
Lin Geng, Dayne Okuhara, Zhiheng Yu, Xin Tian, Yiqiang Cai, Sekiya Shibazaki, Stefan Somlo, Polycystin-2 traffics to cilia independently of polycystin-1 by using an N-terminal RVxP motif Journal of Cell Science. ,vol. 119, pp. 1383- 1395 ,(2006) , 10.1242/JCS.02818
L. Tsiokas, E. Kim, T. Arnould, V. P. Sukhatme, G. Walz, Homo- and heterodimeric interactions between the gene products of PKD1 and PKD2. Proceedings of the National Academy of Sciences of the United States of America. ,vol. 94, pp. 6965- 6970 ,(1997) , 10.1073/PNAS.94.13.6965
Gregory J Pazour, Jovenal T San Agustin, John A Follit, Joel L Rosenbaum, George B Witman, None, Polycystin-2 localizes to kidney cilia and the ciliary level is elevated in orpk mice with polycystic kidney disease Current Biology. ,vol. 12, ,(2002) , 10.1016/S0960-9822(02)00877-1
Rafael Mattera, Cecilia N Arighi, Robert Lodge, Marino Zerial, Juan S Bonifacino, Divalent interaction of the GGAs with the Rabaptin-5-Rabex-5 complex The EMBO Journal. ,vol. 22, pp. 78- 88 ,(2003) , 10.1093/EMBOJ/CDG015
Liyun Sang, Julie J. Miller, Kevin C. Corbit, Rachel H. Giles, Matthew J. Brauer, Edgar A. Otto, Lisa M. Baye, Xiaohui Wen, Suzie J. Scales, Mandy Kwong, Erik G. Huntzicker, Mindan K. Sfakianos, Wendy Sandoval, J. Fernando Bazan, Priya Kulkarni, Francesc R. Garcia-Gonzalo, Allen D. Seol, John F. O'Toole, Susanne Held, Heiko M. Reutter, William S. Lane, Muhammad Arshad Rafiq, Abdul Noor, Muhammad Ansar, Akella Radha Rama Devi, Val C. Sheffield, Diane C. Slusarski, John B. Vincent, Daniel A. Doherty, Friedhelm Hildebrandt, Jeremy F. Reiter, Peter K. Jackson, Mapping the NPHP-JBTS-MKS Protein Network Reveals Ciliopathy Disease Genes and Pathways Cell. ,vol. 145, pp. 513- 528 ,(2011) , 10.1016/J.CELL.2011.04.019
Harald Stenmark, Gaetano Vitale, Oliver Ullrich, Marino Zerial, Rabaptin-5 is a direct effector of the small GTPase Rab5 in endocytic membrane fusion. Cell. ,vol. 83, pp. 423- 432 ,(1995) , 10.1016/0092-8674(95)90120-5