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PMID: 19948498 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Lte1 contributes to Bfa1 localization rather than stimulating nucleotide exchange by Tem1.

The Journal of cell biology ·Vol. 187 ·No. 4 ·2009-11-16 ·Pages 497-511

Geymonat M, Spanos A, de Bettignies G, Sedgwick SG

Abstract

Lte1 is a mitotic regulator long envisaged as a guanosine nucleotide exchange factor (GEF) for Tem1, the small guanosine triphosphatase governing activity of the Saccharomyces cerevisiae mitotic exit network. We demonstrate that this model requires reevaluation. No GEF activity was detectable in vitro, and mutational analysis of Lte1's putative GEF domain indicated that Lte1 activity relies on interaction with Ras for localization at the bud cortex rather than providing nucleotide exchange. Instead, we found that Lte1 can determine the subcellular localization of Bfa1 at spindle pole bodies (SPBs). Under conditions in which Lte1 is essential, Lte1 promoted the loss of Bfa1 from the maternal SPB. Moreover, in cells with a misaligned spindle, mislocalization of Lte1 in the mother cell promoted loss of Bfa1 from one SPB and allowed bypass of the spindle position checkpoint. We observed that lte1 mutants display aberrant localization of the polarity cap, which is the organizer of the actin cytoskeleton. We propose that Lte1's role in cell polarization underlies its contribution to mitotic regulation.

MeSH Terms
Cell Cycle/genetics Cell Polarity/genetics Cytoskeletal Proteins/genetics,metabolism Guanine Nucleotide Exchange Factors/genetics,metabolism,physiology Intracellular Space/genetics,metabolism Mitosis/genetics Monomeric GTP-Binding Proteins/genetics,metabolism Point Mutation Saccharomyces cerevisiae Proteins/genetics,metabolism,physiology Sequence Homology, Nucleic Acid Spindle Apparatus/genetics,metabolism
Chemicals
BFA1 protein, S cerevisiae Cytoskeletal Proteins Guanine Nucleotide Exchange Factors LTE1 protein, S cerevisiae Saccharomyces cerevisiae Proteins TEM1 protein, S cerevisiae Monomeric GTP-Binding Proteins
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Geymonat Marco
Division of Stem Cell Biology and Developmental Genetics, National Institute for Medical Research, London NW7 1AA, England, UK. [email protected]
Spanos Adonis
de Bettignies Geoffroy
Sedgwick Steven G
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Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
1540-8140
DOI
10.1083/jcb.200905114
Email
[email protected]
Published
2009-11-16
Pages
497-511
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2779235
Subset
IM
Grants
Medical Research Council · United Kingdom
External Links
PubMed source DOI: 10.1083/jcb.200905114 PMC Full Text View journal details
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