Abstract
The Lethal giant larvae (Lgl) tumor suppressor family is conserved from yeast to mammals and plays a critical yet controversial role in cell polarity. Studies on Drosophila Lgl suggest that its function in polarity is through regulation of the acto-myosin cytoskeleton. In contrast, studies on the yeast Lgl homologs, Sro7/Sro77, suggest a function in exocytosis through interaction with the t-SNARE Sec9. Using yeast/mammalian Lgl chimeras, we demonstrate that the overall architecture of Lgl proteins is highly conserved and that the C-terminal domain is the major site of SNARE interaction within both yeast and mammalian homologs. Importantly, we find that the ability of Lgl chimeras to function as the only source of Lgl in yeast correlates precisely with the ability to interact with the yeast t-SNARE. We report a novel interaction between Sro7 and the yeast myosin V, Myo2. However, we find that interactions with either Myo2 or Myo1 (myosin II) cannot account for the dramatic functional differences observed for these chimeras in yeast. These results provide the first demonstration that the interaction of an Lgl family member with a specific effector is critical to its function in vivo. These data support the model that the Lgl family functions in cell polarity, at least in part, by regulating SNARE-mediated membrane delivery events at the cell surface.
Publication types
-
Research Support, N.I.H., Extramural
-
Research Support, U.S. Gov't, P.H.S.
MeSH terms
-
Actins / metabolism
-
Adaptor Proteins, Signal Transducing
-
Amino Acid Sequence
-
Animals
-
Binding Sites
-
Carrier Proteins / genetics
-
Carrier Proteins / metabolism*
-
Cell Polarity / genetics
-
Conserved Sequence
-
Drosophila Proteins / genetics
-
Drosophila Proteins / metabolism*
-
Mammals / genetics
-
Membrane Proteins / genetics
-
Membrane Proteins / metabolism
-
Mutation
-
Myosin Heavy Chains / genetics
-
Myosin Heavy Chains / metabolism
-
Myosin Type V / genetics
-
Myosin Type V / metabolism
-
Protein Structure, Tertiary
-
Qc-SNARE Proteins
-
Recombinant Proteins / genetics
-
Recombinant Proteins / metabolism
-
SNARE Proteins
-
Saccharomyces cerevisiae / cytology
-
Saccharomyces cerevisiae / genetics
-
Saccharomyces cerevisiae Proteins / genetics
-
Saccharomyces cerevisiae Proteins / metabolism*
-
Tumor Suppressor Proteins / genetics
-
Tumor Suppressor Proteins / metabolism*
-
Two-Hybrid System Techniques
-
Vesicular Transport Proteins / genetics
-
Vesicular Transport Proteins / metabolism*
Substances
-
Actins
-
Adaptor Proteins, Signal Transducing
-
Carrier Proteins
-
Drosophila Proteins
-
MYO2 protein, S cerevisiae
-
Membrane Proteins
-
Qc-SNARE Proteins
-
Recombinant Proteins
-
SEC9 protein, S cerevisiae
-
SNARE Proteins
-
SRO7 protein, S cerevisiae
-
Saccharomyces cerevisiae Proteins
-
Tumor Suppressor Proteins
-
Vesicular Transport Proteins
-
l(2)gl protein, Drosophila
-
Myosin Type V
-
Myosin Heavy Chains