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Reference - PMID:23457617 - Haploinsufficiency of the Sec7 guanine nucleotide exchange factor gea1 impairs septation in fission yeast.

Reference summary

PubMed ID
PMID:23457617
Title
Haploinsufficiency of the Sec7 guanine nucleotide exchange factor gea1 impairs septation in fission yeast.
Authors
Eckler AM, Wilder C, Castanon A, Ferris VM, Lamere RA, Perrin BA, Pearlman R, White B, Byrd C, Ludvik N, Nichols N, Poole-Sumrall K, Sztul E, Styers ML
Citation
PLoS One 2013;8(2):e56807
Publication year
2013
Abstract
Membrane trafficking is essential to eukaryotic life and is controlled by a complex network of proteins that regulate movement of proteins and lipids between organelles. The GBF1/GEA family of Guanine nucleotide Exchange Factors (GEFs) regulates trafficking between the endoplasmic reticulum and Golgi by catalyzing the exchange of GDP for GTP on ADP Ribosylation Factors (Arfs). Activated Arfs recruit coat protein complex 1 (COP-I) to form vesicles that ferry cargo between these organelles. To further explore the function of the GBF1/GEA family, we have characterized a fission yeast mutant lacking one copy of the essential gene gea1 (gea1+/-), the Schizosaccharomyces pombe ortholog of GBF1. The haploinsufficient gea1+/- strain was shown to be sensitive to the GBF1 inhibitor brefeldin A (BFA) and was rescued from BFA sensitivity by gea1p overexpression. No overt defects in localization of arf1p or arf6p were observed in gea1+/- cells, but the fission yeast homolog of the COP-I cargo sac1 was mislocalized, consistent with impaired COP-I trafficking. Although Golgi morphology appeared normal, a slight increase in vacuolar size was observed in the gea1+/- mutant strain. Importantly, gea1+/- cells exhibited dramatic cytokinesis-related defects, including disorganized contractile rings, an increased septation index, and alterations in septum morphology. Septation defects appear to result from altered secretion of enzymes required for septum dynamics, as decreased secretion of eng1p, a β-glucanase required for septum breakdown, was observed in gea1+/- cells, and overexpression of eng1p suppressed the increased septation phenotype. These observations implicate gea1 in regulation of septum breakdown and establish S. pombe as a model system to explore GBF1/GEA function in cytokinesis.

Annotation

GO biological process

GO:0043001 - Golgi to plasma membrane protein transport

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GO cellular component

GO:0005938 - cell cortex

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GO:0000935 - division septum

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GO:0005783 - endoplasmic reticulum

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GO:0005794 - Golgi apparatus

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Single locus phenotype

FYPO:0000230 - abnormal actomyosin contractile ring actin filament organization

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FYPO:0002719 - decreased protein localization to septum

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FYPO:0000538 - decreased protein secretion during vegetative growth

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FYPO:0000650 - increased septation index

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FYPO:0001406 - increased septum thickness

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FYPO:0000123 - large vacuoles during vegetative growth

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FYPO:0001390 - misoriented septum during vegetative growth

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FYPO:0000426 - normal endocytosis

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FYPO:0002715 - normal Golgi apparatus morphology

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FYPO:0001164 - normal growth on glucose carbon source

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FYPO:0001402 - normal protein localization to cell cortex during vegetative growth

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FYPO:0002332 - normal protein localization to Golgi apparatus

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FYPO:0002717 - normal vacuole fusion during cellular hypotonic response

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FYPO:0002714 - protein mislocalized to Golgi apparatus

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FYPO:0000067 - resistance to brefeldin A

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FYPO:0001450 - resistance to cold

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FYPO:0001379 - resistance to tacrolimus

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FYPO:0001501 - sensitive to brefeldin A

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FYPO:0000086 - sensitive to tacrolimus

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FYPO:0000115 - sensitive to valproic acid

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FYPO:0001496 - viable elongated multiseptate vegetative cell

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