hob1+, the fission yeast homolog of Bin1, is dispensable for endocytosis or actin organization, but required for the response to starvation or genotoxic stress.
BAR (Bin/Amphiphysin/Rvs) adapter proteins have been suggested to regulate endocytosis, actin organization, apoptosis, and transcription, but their precise roles are obscure. There are at least five mammalian genes that encode BAR adapter proteins, including the evolutionarily conserved and ubiquitously expressed Bin1/Amphiphysin-II and Bin3 genes. Bin1 holds special interest as certain splice isoforms localize to the nucleus, interact with the c-Abl and c-Myc oncoproteins, and display tumor suppressor properties. To obtain functional insights, we embarked upon a genetic analysis of the two BAR adapter proteins expressed in the fission yeast Schizosaccharomyces pombe. In a previous work, a role in actin organization and cytokinesis was identified for the Bin3 homolog hob3+. In this study, a role in stress signaling was defined for the Bin1 homolog, hob1+. Notably, hob1+ was dispensable for endocytosis, actin organization, or osmotic sensitivity. Instead, mutation of hob1+ led to slight cell elongation and faulty cell cycle arrest upon nutrient starvation. These defects were complemented by Bin1, but not by Amphiphysin-I, arguing that these genes have distinct functions despite their structural similarity. hob1 delta mutant cells were also hypersensitive to genotoxic stress. This was not related to a faulty checkpoint response, but mutation in the checkpoint gene rad3(+) further exacerbated the sensitivity of hob1 delta mutant cells. Interestingly, mutation of the cell cycle regulator wee1+ partially relieved the sensitivity defect, suggesting that hob1+ may influence the efficiency of DNA repair or checkpoint release after DNA damage. Genetic and biochemical evidence indicated that hob3+ is epistatic to hob1+ in the response to genotoxic stress. Our findings indicate that the Bin1 homolog hob1+ participates in DNA damage signaling and they suggest a novel role for BAR adapter proteins in stress response processes.
Routhier
Eric L
EL
Cancer Research Group, The DuPont Pharmaceuticals Company, Glenolden, PA 19036, USA.
Donover
P Scott
PS
Prendergast
George C
GC
D000199:Actins / Q000502:physiology*; D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D002352:Carrier Proteins / Q000235:genetics* / Q000502:physiology; D018797:Cell Cycle Proteins / Q000502:physiology; D064447:Checkpoint Kinase 2; D003598:Cytoskeletal Proteins; D004249:DNA Damage / Q000502:physiology; D004705:Endocytosis / Q000502:physiology*; D008840:Microfilament Proteins; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics* / Q000502:physiology; D011494:Protein Kinases / Q000502:physiology; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000502:physiology; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000502:physiology; D012568:Schizosaccharomyces / Q000235:genetics* / Q000502:physiology; D029702:Schizosaccharomyces pombe Proteins; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000502:physiology
D000199:Actins; D048868:Adaptor Proteins, Signal Transducing; C101410:BIN1 protein, human; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; D008840:Microfilament Proteins; D009687:Nuclear Proteins; C082282:RVS167 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D029702:Schizosaccharomyces pombe Proteins; D025521:Tumor Suppressor Proteins; C491080:hob1 protein, S pombe; D011494:Protein Kinases; D064447:Checkpoint Kinase 2; C456840:rad3 protein, S pombe