par-1, Atypical pkc, and PP2A/B55 sur-6 Are Implicated in the Regulation of Exocyst-Mediated Membrane Trafficking in Caenorhabditis elegans

被引：6

作者：

Jiu, Yaming ^{[1
]}

Hasygar, Kiran ^{[1
,2
]}

Tang, Lois ^{[5
,6
]}

Liu, Yanbo ^{[1
]}

Holmberg, Carina I. ^{[3
,4
]}

Burglin, Thomas R. ^{[5
,6
]}

Hietakangas, Ville ^{[1
,2
]}

Jantti, Jussi ^{[1
,7
]}

机构：

[1] Univ Helsinki, Inst Biotechnol, Res Program Cell & Mol Biol, Helsinki 00014, Finland

[2] Univ Helsinki, Dept Biosci, FIN-00014 Helsinki, Finland

[3] Univ Helsinki, Res Programs Unit, FIN-00014 Helsinki, Finland

[4] Univ Helsinki, Inst Biomed, FIN-00014 Helsinki, Finland

[5] Karolinska Inst, Novum, Dept Biosci & Nutr, SE-14183 Huddinge, Sweden

[6] Karolinska Inst, Novum, Ctr Biosci, SE-14183 Huddinge, Sweden

[7] VTT Tech Res Ctr Finland, Espoo 02044, Vtt, Finland

来源：

G3-GENES GENOMES GENETICS | 2014年 / 4卷 / 01期

基金：

瑞典研究理事会; 芬兰科学院;

关键词：

pkc-3; par-1; exocyst; PP2A; Caenorhabditis elegans; PHOSPHATASE; 2A; PROTEIN; KINASE; PHOSPHORYLATION; POLARITY; COMPLEX; GROWTH; NEURONS; ORGANIZATION; HOMOLOG;

D O I：

10.1534/g3.113.006718

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

The exocyst is a conserved protein complex that is involved in tethering secretory vesicles to the plasma membrane and regulating cell polarity. Despite a large body of work, little is known how exocyst function is controlled. To identify regulators for exocyst function, we performed a targeted RNA interference (RNAi) screen in Caenorhabditis elegans to uncover kinases and phosphatases that genetically interact with the exocyst. We identified seven kinase and seven phosphatase genes that display enhanced phenotypes when combined with hypomorphic alleles of exoc-7 (exo70), exoc-8 (exo84), or an exoc-7;exoc-8 double mutant. We show that in line with its reported role in exocytotic membrane trafficking, a defective exoc-8 caused accumulation of exocytotic soluble NSF attachment protein receptor (SNARE) proteins in both intestinal and neuronal cells in C. elegans. Down-regulation of the phosphatase protein phosphatase 2A (PP2A) phosphatase regulatory subunit sur-6/B55 gene resulted in accumulation of exocytic SNARE proteins SNB-1 and SNAP-29 in wild-type and in exoc-8 mutant animals. In contrast, RNAi of the kinase par-1 caused reduced intracellular green fluorescent protein signal for the same proteins. Double RNAi experiments for par-1, pkc-3, and sur-6/B55 in C. elegans suggest a possible cooperation and involvement in postembryo lethality, developmental timing, as well as SNARE protein trafficking. Functional analysis of the homologous kinases and phosphatases in Drosophila median neurosecretory cells showed that atypical protein kinase C kinase and phosphatase PP2A regulate exocyst-dependent, insulin-like peptide secretion. Collectively, these results characterize kinases and phosphatases implicated in the regulation of exocyst function, and suggest the possibility for interplay between the par-1 and pkc-3 kinases and the PP2A phosphatase regulatory subunit sur-6 in this process.

引用

页码：173 / 183

页数：11