灰霉病菌中2C型丝氨酸/苏氨酸磷酸酶（PTCs）及酪氨酸磷酸酶（PTPs）的功能研究
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摘要
由激酶及磷酸酶催化的蛋白磷酸化与去磷酸化反应参与了生物体的多个代谢过程。真核生物蛋白的磷酸化位点主要有丝氨酸、苏氨酸及酪氨酸残基,因此,相应的去磷酸化过程是由丝氨酸/苏氨酸磷酸酶或酪氨酸磷酸酶催化完成。2C型丝氨酸/苏氨酸磷酸酶(PP2Cs)及酪氨酸磷酸酶(PTPs)是十分重要的两类磷酸酶,参与调控生物体内的多个生命活动过程,但是,目前这些磷酸酶在丝状真菌中的研究仍然处于起步阶段。
灰霉病菌(Botrytis cinerea)的基因组中存在5个2C型丝氨酸/苏氨酸磷酸酶(PP2Cs)基因(命名为BcPTC1,-3,-5,-6和-7)和两个酪氨酸磷酸酶基因(BcPTPA和BcPTPB).本文通过基因敲除及回补的方法研究了这些基因的生物学功能,结果发现,BcPTC5, BcPTC6和BcPTC7基因突变体的表型与野生型相比变化不明显,但是另外4个基因(BcPTC1, BcPTC3, BcPTPA和BcPTPB)的突变体的表型与野生亲本菌株相比发生了显著变化：1)四个基因突变体均不能产生菌核,除BcPtpB突变体以外,另三个基因突变体的生长速率明显下降。2)BcPtpA突变体的分生孢子数目显著减少,而其它三个基因突变体的分生孢子产生量明显增多。3)这四个基因敲除体的黑色素合成均显著增加。4)四个基因的敲除突变体对渗透压力(NaCl和KC1)、氧化压力(H2O2)、DCFs药剂(iprodione)及细胞壁损伤物质(刚果红、咖啡因及细胞壁降解酶)都表现一定程度的敏感。5)在酵母中Ptcl, Ptc3, Ptp2及Ptp3均可以负向调控HOG (high-osmolarity glycerol)及CWI (the cell wall integrity)信号途径,在灰霉病菌中只有BcPtc3是HOG信号途径的负调控元件；另外,BcPtc1和BcPtc3也可以正向调控灰霉BcBmp3(与酵母CWI信号途径中的Mpk1/Slt2同源)蛋白的磷酸化；与酵母中Ptp2/3作用不同,灰霉中两个酪氨酸磷酸酶BcPtpA和BcPtpB能够正向调控BcBmp3和BcSakl的磷酸化。6)四个基因的敲除突变体在黄瓜、油菜、番茄叶片,苹果等寄主上的致病力明显下降。这些结果表明, BcPtc1, BcPtc3, BcPtpA及BcPtpB在灰霉病菌的菌丝生长、分化、致病以及对适应外界胁迫中发挥重要作用。
Protein phosphorylation and dephosphorylation executed by protein kinases and protein phosphatases, respectively, is a major mechanism regulating many cellular processes. Most phosphorylation events in eukaryotes occur at serine, threonine and tyrosine residues. Accordingly, removal of the phosphates is catalyzed by protein Ser/Thr phosphatases or tyrosine phosphatases. Type2C Ser/Thr phosphatases (PP2Cs) and tyrosine phosphatases (PTPs) are involved in a large variety of regulatory processes in many eukaryotes, but little has been known about their functions in filamentous fungi.
Botrytis cinerea contains five putative PP2C genes, named BcPTCl,-3,-5,-6and-7, and two putative protein tyrosine phosphatase (PTP) genes (BcPTPA and BcPTPB). Biological functions of these genes were analyzed by gene deletion and complementation. While no phenotypes aberrant from the wild type were observed with mutants of BcPtc5, BcPtc6and BcPtc7, mutants of BcPtc1, BcPtc3, BcPtpA and BcPtpB showed significant phenotype changes, indicating that these four genes play important roles in B. cinerea. Results of this study showed that1) BcPtc1, BcPtc3, BcPtpA and BcPtpB regulate vegetative differentiation. Mutants of all the four genes could not produce any sclerotium. All the mutants had reduced hyphal growth rate except BcPtpB.2) In addition, increased conidiation were observed in BcPtcl, BcPtc3, and BcPtpB mutants, while mutant of BcPtpA had reduced conidiation.3) BcPtc1, BcPtc3, BcPtpA and BcPtpB were involved in regulation of hypal melanization. Disruption of the four genes all led to increased pigmentation and the pigment was confirmed as melanin.4) They exhibited increased sensitivity to osmotic stress mediated by NaCl and KC1, to oxidative stress generated by H2O2, to DCFs fungicides (iprodione) and to cell wall damaging agents (Congo red, caffeine and the cell wall degrading enzyme).5) In S. cerevisiae, Ptc1, Ptc3, Ptp2and Ptp3negatively regulate the high-osmolarity glycerol (HOG) pathway and the cell wall integrity (CWI) pathway. In B. cinerea, however, BcPtc3, but not BcPtcl, negatively regulates phosphorylation of BcSakl (the homologue of Hog1) although both BcPTCl and BcPTC3were able to rescue the growth defects of a yeast PTC1deletion mutant under various stress conditions. Moreover, deletion of BcPTCl or BcPTC3led to decreased phosphorylation of the mitogen-activated protein (MAP) kinase BcBmp3(a homologue of Saccharomyces cerevisiae Mpkl/Slt2in the CWI pathway). In contrast to S. cerevisiae, BcPtpA and BcPtpB positively regulate phosphorylation of BcSak1(the homologue of Hog1) and BcBmp3in B. cinerea.6) All the mutants exhibited dramatically decreased virulence on cucumber, rapeseed or tomato leaves, apples and grapes. These results demonstrated that BcPtc1, BcPtc3, BcPtpA and BcPtpB play important roles in the regulation of hyphal growth, vegetative differentiation, virulence and multi-stress tolerance in Botrytis cinerea.
灰霉病菌(Botrytis cinerea)的基因组中存在5个2C型丝氨酸/苏氨酸磷酸酶(PP2Cs)基因(命名为BcPTC1,-3,-5,-6和-7)和两个酪氨酸磷酸酶基因(BcPTPA和BcPTPB).本文通过基因敲除及回补的方法研究了这些基因的生物学功能,结果发现,BcPTC5, BcPTC6和BcPTC7基因突变体的表型与野生型相比变化不明显,但是另外4个基因(BcPTC1, BcPTC3, BcPTPA和BcPTPB)的突变体的表型与野生亲本菌株相比发生了显著变化：1)四个基因突变体均不能产生菌核,除BcPtpB突变体以外,另三个基因突变体的生长速率明显下降。2)BcPtpA突变体的分生孢子数目显著减少,而其它三个基因突变体的分生孢子产生量明显增多。3)这四个基因敲除体的黑色素合成均显著增加。4)四个基因的敲除突变体对渗透压力(NaCl和KC1)、氧化压力(H2O2)、DCFs药剂(iprodione)及细胞壁损伤物质(刚果红、咖啡因及细胞壁降解酶)都表现一定程度的敏感。5)在酵母中Ptcl, Ptc3, Ptp2及Ptp3均可以负向调控HOG (high-osmolarity glycerol)及CWI (the cell wall integrity)信号途径,在灰霉病菌中只有BcPtc3是HOG信号途径的负调控元件；另外,BcPtc1和BcPtc3也可以正向调控灰霉BcBmp3(与酵母CWI信号途径中的Mpk1/Slt2同源)蛋白的磷酸化；与酵母中Ptp2/3作用不同,灰霉中两个酪氨酸磷酸酶BcPtpA和BcPtpB能够正向调控BcBmp3和BcSakl的磷酸化。6)四个基因的敲除突变体在黄瓜、油菜、番茄叶片,苹果等寄主上的致病力明显下降。这些结果表明, BcPtc1, BcPtc3, BcPtpA及BcPtpB在灰霉病菌的菌丝生长、分化、致病以及对适应外界胁迫中发挥重要作用。
Protein phosphorylation and dephosphorylation executed by protein kinases and protein phosphatases, respectively, is a major mechanism regulating many cellular processes. Most phosphorylation events in eukaryotes occur at serine, threonine and tyrosine residues. Accordingly, removal of the phosphates is catalyzed by protein Ser/Thr phosphatases or tyrosine phosphatases. Type2C Ser/Thr phosphatases (PP2Cs) and tyrosine phosphatases (PTPs) are involved in a large variety of regulatory processes in many eukaryotes, but little has been known about their functions in filamentous fungi.
Botrytis cinerea contains five putative PP2C genes, named BcPTCl,-3,-5,-6and-7, and two putative protein tyrosine phosphatase (PTP) genes (BcPTPA and BcPTPB). Biological functions of these genes were analyzed by gene deletion and complementation. While no phenotypes aberrant from the wild type were observed with mutants of BcPtc5, BcPtc6and BcPtc7, mutants of BcPtc1, BcPtc3, BcPtpA and BcPtpB showed significant phenotype changes, indicating that these four genes play important roles in B. cinerea. Results of this study showed that1) BcPtc1, BcPtc3, BcPtpA and BcPtpB regulate vegetative differentiation. Mutants of all the four genes could not produce any sclerotium. All the mutants had reduced hyphal growth rate except BcPtpB.2) In addition, increased conidiation were observed in BcPtcl, BcPtc3, and BcPtpB mutants, while mutant of BcPtpA had reduced conidiation.3) BcPtc1, BcPtc3, BcPtpA and BcPtpB were involved in regulation of hypal melanization. Disruption of the four genes all led to increased pigmentation and the pigment was confirmed as melanin.4) They exhibited increased sensitivity to osmotic stress mediated by NaCl and KC1, to oxidative stress generated by H2O2, to DCFs fungicides (iprodione) and to cell wall damaging agents (Congo red, caffeine and the cell wall degrading enzyme).5) In S. cerevisiae, Ptc1, Ptc3, Ptp2and Ptp3negatively regulate the high-osmolarity glycerol (HOG) pathway and the cell wall integrity (CWI) pathway. In B. cinerea, however, BcPtc3, but not BcPtcl, negatively regulates phosphorylation of BcSakl (the homologue of Hog1) although both BcPTCl and BcPTC3were able to rescue the growth defects of a yeast PTC1deletion mutant under various stress conditions. Moreover, deletion of BcPTCl or BcPTC3led to decreased phosphorylation of the mitogen-activated protein (MAP) kinase BcBmp3(a homologue of Saccharomyces cerevisiae Mpkl/Slt2in the CWI pathway). In contrast to S. cerevisiae, BcPtpA and BcPtpB positively regulate phosphorylation of BcSak1(the homologue of Hog1) and BcBmp3in B. cinerea.6) All the mutants exhibited dramatically decreased virulence on cucumber, rapeseed or tomato leaves, apples and grapes. These results demonstrated that BcPtc1, BcPtc3, BcPtpA and BcPtpB play important roles in the regulation of hyphal growth, vegetative differentiation, virulence and multi-stress tolerance in Botrytis cinerea.
引文
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