Dysregulated Arl1, a regulator of post-Golgi vesicle tethering, can inhibit endosomal transport and cell proliferation in yeast

被引:18
作者
Benjamin, Jeremy J. R. [1 ]
Poon, Pak P. [1 ,2 ]
Drysdale, John D. [1 ]
Wang, Xiangmin [2 ]
Singer, Richard A. [2 ]
Johnston, Gerald C. [1 ]
机构
[1] Dalhousie Univ, Dept Microbiol & Immunol, Halifax, NS B3H 1X5, Canada
[2] Dalhousie Univ, Dept Biochem & Mol Biol, Halifax, NS B3H 1X5, Canada
基金
加拿大健康研究院;
关键词
D O I
10.1091/mbc.E10-09-0765
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Small monomeric G proteins regulated in part by GTPase-activating proteins (GAPs) are molecular switches for several aspects of vesicular transport. The yeast Gcs1 protein is a dual-specificity GAP for ADP-ribosylation factor (Arf) and Arf-like (Arl)1 G proteins, and also has GAP-independent activities. The absence of Gcs1 imposes cold sensitivity for growth and endosomal transport; here we present evidence that dysregulated Arl1 may cause these impairments. We show that gene deletions affecting the Arl1 or Ypt6 vesicle-tethering pathways prevent Arl1 activation and membrane localization, and restore growth and trafficking in the absence of Gcs1. A mutant version of Gcs1 deficient for both ArfGAP and Arl1GAP activity in vitro still allows growth and endosomal transport, suggesting that the function of Gcs1 that is required for these processes is independent of GAP activity. We propose that, in the absence of this GAP-independent regulation by Gcs1, the resulting dysregulated Arl1 prevents growth and impairs endosomal transport at low temperatures. In cells with dysregulated Arl1, an increased abundance of the Arl1 effector Imh1 restores growth and trafficking, and does so through Arl1 binding. Protein sequestration at the trans-Golgi membrane by dysregulated, active Arl1 may therefore be the mechanism of inhibition.
引用
收藏
页码:2337 / 2347
页数:11
相关论文
共 58 条
[1]   Activation of ADP-ribosylation factor 1 GTPase-activating protein by phosphatidylcholine-derived diacylglycerols [J].
Antonny, B ;
Huber, I ;
Paris, S ;
Chabre, M ;
Cassel, D .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (49) :30848-30851
[2]   ISOLATION AND PHENOTYPIC ANALYSIS OF CONDITIONAL-LETHAL, LINKER-INSERTION MUTATIONS IN THE GENE ENCODING THE LARGEST SUBUNIT OF RNA POLYMERASE-II IN SACCHAROMYCES-CEREVISIAE [J].
ARCHAMBAULT, J ;
DREBOT, MA ;
STONE, JC ;
FRIESEN, JD .
MOLECULAR & GENERAL GENETICS, 1992, 232 (03) :408-414
[3]   A novel Rab6-interacting domain defines a family of Golgi-targeted coiled-coil proteins [J].
Barr, FA .
CURRENT BIOLOGY, 1999, 9 (07) :381-384
[4]   The COPI system: Molecular mechanisms and function [J].
Beck, R. ;
Ravet, M. ;
Wieland, F. T. ;
Cassel, D. .
FEBS LETTERS, 2009, 583 (17) :2701-2709
[5]   Targeting of the arf-like GTPase Arl3p to the Golgi requires N-terminal acetylation and the membrane protein Sys1p [J].
Behnia, R ;
Panic, B ;
Whyte, JRC ;
Munro, S .
NATURE CELL BIOLOGY, 2004, 6 (05) :405-+
[6]   The Yeast Arf GTPase-activating Protein Age1 Is Regulated by Phospholipase D for Post-Golgi Vesicular Transport [J].
Benjamin, Jeremy J. R. ;
Poon, Pak P. ;
Lewis, Stephen M. ;
Auger, Andreanne ;
Wong, Tania A. ;
Singer, Richard A. ;
Johnston, Gerald C. .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2011, 286 (07) :5187-5196
[7]   Ric1p and the Ypt6p GTPase function in a common pathway required for localization of trans-Golgi network membrane proteins [J].
Bensen, ES ;
Yeung, BG ;
Payne, GS .
MOLECULAR BIOLOGY OF THE CELL, 2001, 12 (01) :13-26
[8]   ARF PROTEINS - THE MEMBRANE TRAFFIC POLICE [J].
BOMAN, AL ;
KAHN, RA .
TRENDS IN BIOCHEMICAL SCIENCES, 1995, 20 (04) :147-150
[9]   Genomic screen for vacuolar protein sorting genes in Saccharomyces cerevisiae [J].
Bonangelino, CJ ;
Chavez, EM ;
Bonifacino, JS .
MOLECULAR BIOLOGY OF THE CELL, 2002, 13 (07) :2486-2501
[10]   The mechanisms of vesicle budding and fusion [J].
Bonifacino, JS ;
Glick, BS .
CELL, 2004, 116 (02) :153-166