MHO1, an evolutionarily conserved gene, is synthetic lethal with PLC1; Mho1p has a role in invasive growth.

The novel protein Memo (Mediator of ErbB2 driven cell motility) was identified in a screen for ErbB2 interacting proteins and found to have an essential function in cell motility. Memo is evolutionarily conserved with homologs found in all branches of life; the human and yeast proteins have a simila...

Full description

Bibliographic Details
Main Authors: Ivan D Schlatter, Maria Meira, Vanessa Ueberschlag, Dominic Hoepfner, Rao Movva, Nancy E Hynes
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2012-01-01
Series:PLoS ONE
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22412880/?tool=EBI
id doaj-1ffbb4a8ae1f495dbfc43cf589230446
record_format Article
spelling doaj-1ffbb4a8ae1f495dbfc43cf5892304462021-06-19T05:04:36ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0173e3250110.1371/journal.pone.0032501MHO1, an evolutionarily conserved gene, is synthetic lethal with PLC1; Mho1p has a role in invasive growth.Ivan D SchlatterMaria MeiraVanessa UeberschlagDominic HoepfnerRao MovvaNancy E HynesThe novel protein Memo (Mediator of ErbB2 driven cell motility) was identified in a screen for ErbB2 interacting proteins and found to have an essential function in cell motility. Memo is evolutionarily conserved with homologs found in all branches of life; the human and yeast proteins have a similarity of >50%. In the present study we used the model organism S. cerevisiae to characterize the Memo-homologue Mho1 (Yjr008wp) and to investigate its function in yeast. In a synthetic lethal screen we found MHO1 as a novel synthetic lethal partner of PLC1, which encodes the single phospholipase C in yeast. Double-deleted cells lacking MHO1 and PLC1, proliferate for up to ten generations. Introduction of human Memo into the memoΔplc1Δ strain rescued the synthetic lethal phenotype suggesting that yeast and human proteins have similar functions. Mho1 is present in the cytoplasm and the nucleus of yeast cells; the same distribution of Memo was found in mammalian cells. None of the Memo homologues have a characteristic nuclear localization sequence, however, a conserved nuclear export sequence is found in all. In mammalian cells, blocking nuclear export with Leptomycin B led to nuclear Memo accumulation, suggesting that it is actively exported from the nucleus. In yeast MHO1 expression is induced by stress conditions. Since invasive growth in S. cerevisiea is also stress-induced, we tested Mho1's role in this response. MHO1 deletion had no effect on invasion induced by nutrient deprivation, however, Mho1 overexpression blocked the invasive ability of yeast cells, suggesting that Mho1 might be acting in a dominant negative manner. Taken together, our results show that MHO1 is a novel synthetic lethal interactor with PLC1, and that both gene products are required for proliferation. Moreover, a role for Memo in cell motility/invasion appears to be conserved across species.https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22412880/?tool=EBI
collection DOAJ
language English
format Article
sources DOAJ
author Ivan D Schlatter
Maria Meira
Vanessa Ueberschlag
Dominic Hoepfner
Rao Movva
Nancy E Hynes
spellingShingle Ivan D Schlatter
Maria Meira
Vanessa Ueberschlag
Dominic Hoepfner
Rao Movva
Nancy E Hynes
MHO1, an evolutionarily conserved gene, is synthetic lethal with PLC1; Mho1p has a role in invasive growth.
PLoS ONE
author_facet Ivan D Schlatter
Maria Meira
Vanessa Ueberschlag
Dominic Hoepfner
Rao Movva
Nancy E Hynes
author_sort Ivan D Schlatter
title MHO1, an evolutionarily conserved gene, is synthetic lethal with PLC1; Mho1p has a role in invasive growth.
title_short MHO1, an evolutionarily conserved gene, is synthetic lethal with PLC1; Mho1p has a role in invasive growth.
title_full MHO1, an evolutionarily conserved gene, is synthetic lethal with PLC1; Mho1p has a role in invasive growth.
title_fullStr MHO1, an evolutionarily conserved gene, is synthetic lethal with PLC1; Mho1p has a role in invasive growth.
title_full_unstemmed MHO1, an evolutionarily conserved gene, is synthetic lethal with PLC1; Mho1p has a role in invasive growth.
title_sort mho1, an evolutionarily conserved gene, is synthetic lethal with plc1; mho1p has a role in invasive growth.
publisher Public Library of Science (PLoS)
series PLoS ONE
issn 1932-6203
publishDate 2012-01-01
description The novel protein Memo (Mediator of ErbB2 driven cell motility) was identified in a screen for ErbB2 interacting proteins and found to have an essential function in cell motility. Memo is evolutionarily conserved with homologs found in all branches of life; the human and yeast proteins have a similarity of >50%. In the present study we used the model organism S. cerevisiae to characterize the Memo-homologue Mho1 (Yjr008wp) and to investigate its function in yeast. In a synthetic lethal screen we found MHO1 as a novel synthetic lethal partner of PLC1, which encodes the single phospholipase C in yeast. Double-deleted cells lacking MHO1 and PLC1, proliferate for up to ten generations. Introduction of human Memo into the memoΔplc1Δ strain rescued the synthetic lethal phenotype suggesting that yeast and human proteins have similar functions. Mho1 is present in the cytoplasm and the nucleus of yeast cells; the same distribution of Memo was found in mammalian cells. None of the Memo homologues have a characteristic nuclear localization sequence, however, a conserved nuclear export sequence is found in all. In mammalian cells, blocking nuclear export with Leptomycin B led to nuclear Memo accumulation, suggesting that it is actively exported from the nucleus. In yeast MHO1 expression is induced by stress conditions. Since invasive growth in S. cerevisiea is also stress-induced, we tested Mho1's role in this response. MHO1 deletion had no effect on invasion induced by nutrient deprivation, however, Mho1 overexpression blocked the invasive ability of yeast cells, suggesting that Mho1 might be acting in a dominant negative manner. Taken together, our results show that MHO1 is a novel synthetic lethal interactor with PLC1, and that both gene products are required for proliferation. Moreover, a role for Memo in cell motility/invasion appears to be conserved across species.
url https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22412880/?tool=EBI
work_keys_str_mv AT ivandschlatter mho1anevolutionarilyconservedgeneissyntheticlethalwithplc1mho1phasaroleininvasivegrowth
AT mariameira mho1anevolutionarilyconservedgeneissyntheticlethalwithplc1mho1phasaroleininvasivegrowth
AT vanessaueberschlag mho1anevolutionarilyconservedgeneissyntheticlethalwithplc1mho1phasaroleininvasivegrowth
AT dominichoepfner mho1anevolutionarilyconservedgeneissyntheticlethalwithplc1mho1phasaroleininvasivegrowth
AT raomovva mho1anevolutionarilyconservedgeneissyntheticlethalwithplc1mho1phasaroleininvasivegrowth
AT nancyehynes mho1anevolutionarilyconservedgeneissyntheticlethalwithplc1mho1phasaroleininvasivegrowth
_version_ 1721371454261428224