Lethal giant larvae proteins interact with the exocyst complex and are involved in polarized exocytosis.
The tumor suppressor lethal giant larvae (Lgl) plays a critical role in epithelial cell polarization. However, the molecular mechanism by which Lgl carries out its functions is unclear. In this study, we report that the yeast Lgl proteins Sro7p and Sro77p directly interact with Exo84p, which is a component of the exocyst complex that is essential for targeting vesicles to specific sites of the plasma membrane for exocytosis, and that this interaction is important for post-Golgi secretion. Genetic analyses demonstrate a molecular pathway from Rab and Rho GTPases through the exocyst and Lgl to SNAREs, which mediate membrane fusion. We also found that overexpression of Lgl and t-SNARE proteins not only improves exocytosis but also rescues polarity defects in exocyst mutants. We propose that, although Lgl is broadly distributed in the cells, its localized interaction with the exocyst and kinetic activation are important for the establishment and reenforcement of cell polarity.
Zhang
Xiaoyu
X
Department of Biology, University of Pennsylvania, Philadelphia, PA 19104, USA.
Wang
Puyue
P
Gangar
Akanksha
A
Zhang
Jian
J
Brennwald
Patrick
P
TerBush
Daniel
D
Guo
Wei
W
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism / Q000648:ultrastructure; D016764:Cell Polarity; D005089:Exocytosis; D008561:Membrane Fusion; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D046529:Microscopy, Electron, Transmission; D009154:Mutation; D011485:Protein Binding; D050600:SNARE Proteins; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D015398:Signal Transduction; D033921:Vesicular Transport Proteins / Q000096:biosynthesis; D020691:rab GTP-Binding Proteins / Q000502:physiology; D020741:rho GTP-Binding Proteins / Q000502:physiology
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C120810:EXO84 protein, S cerevisiae; D008565:Membrane Proteins; D050600:SNARE Proteins; C116430:SRO7 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D033921:Vesicular Transport Proteins; C064320:SEC4 protein, S cerevisiae; C074647:RHO3 protein, S cerevisiae; D020691:rab GTP-Binding Proteins; D020741:rho GTP-Binding Proteins