A proteolytic pathway coordinates cell division and heterocyst differentiation in the cyanobacterium Anabaena sp. PCC 7120.
A proteolytic pathway coordinates cell division and heterocyst differentiation in the cyanobacterium Anabaena sp. PCC 7120.
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DOI：
10.1073/pnas.2207963119
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发表时间：
2022-09-06
影响因子：
11.1
通讯作者：
中科院分区：
文献类型：
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蛋白质降解是生物学中一种重要的调控机制。虽然HetF一直被认为是丝状蓝藻Anabaena sp. PCC 7120中的一种假定的蛋白酶，但其活性或底物从未被证实。在本研究中，我们提供了HetF作为特异性底物作用于PatU3的蛋白酶活性的体外和体内证据。HetF对PatU3的降解可以缓解PatU3对细胞分裂和异囊发育的抑制作用，从而为这两个生物学过程的协调提供了机制。本文报道的蛋白水解系统丰富了我们对蓝藻细胞分裂和发育的控制机制的认识。丝状多细胞蓝藻Anabaena sp. PCC 7120 （Anabaena）是研究细胞分化和细胞间相互作用的原核模型。在联合氮剥夺后，水藻形成一种特殊的细胞类型，异囊，用于好氧固氮。异囊在营养细胞间呈半规则间隔。异囊分化与细胞分裂偶联，但其机制尚不清楚。这一机制可能是由蛋白酶HetF介导的，它是一种分裂成分，是杂种囊分化所必需的。在本研究中，通过抑制因子筛选，我们发现PatU3是HetF下游的一个负调节因子，作用于细胞分裂和异囊发育。在ΔhetF突变体中，失活patU3恢复了细胞分裂和异囊分化的能力，而在野生型背景下，过表达patU3抑制了这两个过程。我们证明了PatU3是HetF蛋白酶活性的特定底物。因此，PatU3在hetf缺陷突变体中积累，这是导致突变表型的原因。PatU3被HetF切割的位点位于Arg117残基之后，Arg117残基的突变使PatU3对HetF加工产生抗性，并模拟了HetF缺失的效果。我们的研究结果证明，HetF通过控制PatU3的抑制作用来调节细胞分裂和异囊分化。在发育生物学和多细胞研究中，这种蛋白水解途径在原核生物模型中构成了细胞分裂和分化的协调机制。
Protein degradation is an important regulation mechanism in biology. Although HetF has long been predicted to be a putative protease in the filamentous cyanobacterium Anabaena sp. PCC 7120, its activity or substrate has never been demonstrated. In this study, we provided in vitro and in vivo evidence for the protease activity of HetF acting on PatU3 as a specific substrate. The degradation of PatU3 by HetF relieves the inhibitory effects of PatU3 on cell division and heterocyst development, thus providing a mechanism for the coordination of the two biological processes. The proteolytic system reported here enriched our understanding on the control mechanism for cell division and development in cyanobacteria. The filamentous, multicellular cyanobacterium Anabaena sp. PCC 7120 (Anabaena) is a prokaryotic model for the study of cell differentiation and cell-cell interactions. Upon combined-nitrogen deprivation, Anabaena forms a particular cell type, heterocyst, for aerobic nitrogen fixation. Heterocysts are semiregularly spaced among vegetative cells. Heterocyst differentiation is coupled to cell division, but the underlying mechanism remains unclear. This mechanism could be mediated by the putative protease HetF, which is a divisome component and is necessary for heterocyst differentiation. In this study, by suppressor screening, we identified PatU3, as a negative regulator acting downstream of HetF for cell division and heterocyst development. The inactivation of patU3 restored the capacity of cell division and heterocyst differentiation in the ΔhetF mutant, and overexpression of patU3 inhibited both processes in the wild-type background. We demonstrated that PatU3 was a specific substrate of the protease activity of HetF. Consequently, PatU3 accumulated in the hetF-deficient mutant, which was responsible for the resultant mutant phenotype. The cleavage site of PatU3 by HetF was mapped after the Arg117 residue, whose mutation made PatU3 resistant to HetF processing, and mimicked the effect of hetF deletion. Our results provided evidence that HetF regulated cell division and heterocyst differentiation by controlling the inhibitory effects of PatU3. This proteolytic pathway constituted a mechanism for the coordination between cell division and differentiation in a prokaryotic model used for studies on developmental biology and multicellularity.
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影响因子：
2.9
作者：
Gorelova, O. A.;Baulina, O. I.;Koksharova, O. A.
通讯作者：
Koksharova, O. A.
DOI：
10.1073/pnas.1207530109
发表时间：
2012-09-18
影响因子：
11.1
作者：
Risser, Douglas D.;Wong, Francis C. Y.;Meeks, John C.
通讯作者：
Meeks, John C.
影响因子：
3.2
作者：
Du, Ye;Cai, Yan;Xu, Xudong
通讯作者：
Xu, Xudong
影响因子：
4.7
作者：
Niu, Tian-Cai;Lin, Gui-Ming;Zhang, Cheng-Cai
通讯作者：
Zhang, Cheng-Cai
影响因子：
4.2
作者：
Flaherty BL;Johnson DB;Golden JW
通讯作者：
Golden JW